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Kizzmekia Corbett Presentation at NIH - June 5th, 2019

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  14. <p begin="00:00:05.63" end="00:00:11.13" region="speaker"><metadata ccrow="14" cccol="0"/>I&apos;M BERNIE GRAHAM, CHIEF OF THE</p>
  15. <p begin="00:00:11.13" end="00:00:14.07" region="speaker"><metadata ccrow="14" cccol="0"/>ORAL PATHOGENESIS LAB AT THE VRC</p>
  16. <p begin="00:00:14.07" end="00:00:16.67" region="speaker"><metadata ccrow="14" cccol="2"/>AND MY PLEASURE TO INTRODUCE</p>
  17. <p begin="00:00:16.67" end="00:00:18.00" region="speaker"><metadata ccrow="14" cccol="2"/>DR. KIZZMEKIA CORBETT TODAY.</p>
  18. <p begin="00:00:18.00" end="00:00:20.23" region="speaker"><metadata ccrow="14" cccol="0"/>I FIRST MET DR. CORBETT WHEN SHE</p>
  19. <p begin="00:00:20.23" end="00:00:25.43" region="speaker"><metadata ccrow="14" cccol="1"/>WAS A MIRE SCHOLAR AT UNBC AND</p>
  20. <p begin="00:00:25.43" end="00:00:27.27" region="speaker"><metadata ccrow="14" cccol="3"/>THEN IN THE UNDERGRADUATE</p>
  21. <p begin="00:00:27.27" end="00:00:29.43" region="speaker"><metadata ccrow="14" cccol="0"/>SCHOLARSHIP PROGRAM HERE AT NIH</p>
  22. <p begin="00:00:29.43" end="00:00:32.63" region="speaker"><metadata ccrow="14" cccol="2"/>SHE THEN WENT ON TO GET HER</p>
  23. <p begin="00:00:32.63" end="00:00:38.60" region="speaker"><metadata ccrow="14" cccol="1"/>DOCTORAL TRAINING AT UNC UNDER</p>
  24. <p begin="00:00:38.60" end="00:00:41.83" region="speaker"><metadata ccrow="14" cccol="2"/>ARAVENDA, SHE WORKED ON RSV,</p>
  25. <p begin="00:00:41.83" end="00:00:44.73" region="speaker"><metadata ccrow="14" cccol="2"/>INFLUENZA, FLAVI VIRUSES AND</p>
  26. <p begin="00:00:44.73" end="00:00:46.73" region="speaker"><metadata ccrow="14" cccol="8"/>CORONA VIRUSES.</p>
  27. <p begin="00:00:46.73" end="00:00:50.73" region="speaker"><metadata ccrow="14" cccol="0"/>WHEN I FIRST MET DR. CORBETT, I</p>
  28. <p begin="00:00:50.73" end="00:00:52.67" region="speaker"><metadata ccrow="14" cccol="0"/>ASKED HER WHAT SHE WANTED TO DO</p>
  29. <p begin="00:00:52.67" end="00:00:54.90" region="speaker"><metadata ccrow="14" cccol="2"/>IN HER CAREER AND SHE SAID I</p>
  30. <p begin="00:00:54.90" end="00:00:58.13" region="speaker"><metadata ccrow="14" cccol="5"/>WANT TO TAKE YOUR JOB.</p>
  31. <p begin="00:00:58.13" end="00:01:02.00" region="speaker"><metadata ccrow="14" cccol="5"/>AND I SAID WELL, OKAY.</p>
  32. <p begin="00:01:02.00" end="00:01:05.33" region="speaker"><metadata ccrow="14" cccol="0"/>WHAT&apos;S BEEN FUN FOR ME TO SEE IS</p>
  33. <p begin="00:01:05.33" end="00:01:08.93" region="speaker"><metadata ccrow="14" cccol="1"/>THAT AS SHE&apos;S PROGRESSED IN A</p>
  34. <p begin="00:01:08.93" end="00:01:10.27" region="speaker"><metadata ccrow="14" cccol="0"/>VERY DELIBERATE WAY, SHE WANTED</p>
  35. <p begin="00:01:10.27" end="00:01:12.13" region="speaker"><metadata ccrow="14" cccol="2"/>TO BE A BASIC SCIENTIST, SHE</p>
  36. <p begin="00:01:12.13" end="00:01:13.93" region="speaker"><metadata ccrow="14" cccol="2"/>DIDN&apos;T REALLY WANT TO GO TO</p>
  37. <p begin="00:01:13.93" end="00:01:15.33" region="speaker"><metadata ccrow="14" cccol="8"/>MEDICAL SCHOOL.</p>
  38. <p begin="00:01:15.33" end="00:01:17.47" region="speaker"><metadata ccrow="14" cccol="0"/>AND EVEN THOUGH SHE&apos;S BEEN VERY</p>
  39. <p begin="00:01:17.47" end="00:01:20.87" region="speaker"><metadata ccrow="14" cccol="4"/>DEVOTED TO MENTORING AND</p>
  40. <p begin="00:01:20.87" end="00:01:21.77" region="speaker"><metadata ccrow="14" cccol="0"/>INSTITUTIONAL SERVICE AND THINGS</p>
  41. <p begin="00:01:21.77" end="00:01:27.00" region="speaker"><metadata ccrow="14" cccol="0"/>LIKE THAT, SHE&apos;S MORE DEVOTED TO</p>
  42. <p begin="00:01:27.00" end="00:01:29.87" region="speaker"><metadata ccrow="14" cccol="2"/>SCIENCE AND BIOLOGY AND JUST</p>
  43. <p begin="00:01:29.87" end="00:01:32.87" region="speaker"><metadata ccrow="14" cccol="3"/>GETTING THE SCIENCE RIGHT.</p>
  44. <p begin="00:01:32.87" end="00:01:36.83" region="speaker"><metadata ccrow="14" cccol="0"/>SO THERE&apos;S VERY FEW THINGS LESS</p>
  45. <p begin="00:01:36.83" end="00:01:38.43" region="speaker"><metadata ccrow="14" cccol="0"/>GRATIFYING, VERY FEW THINGS MORE</p>
  46. <p begin="00:01:38.43" end="00:01:41.13" region="speaker"><metadata ccrow="14" cccol="4"/>GRATIFYING THAN TO WATCH</p>
  47. <p begin="00:01:41.13" end="00:01:42.87" region="speaker"><metadata ccrow="14" cccol="0"/>SOMEBODY FULFILL THEIR DESTINY.</p>
  48. <p begin="00:01:42.87" end="00:01:45.57" region="speaker"><metadata ccrow="14" cccol="0"/>I THINK THAT&apos;S WHAT SHE&apos;S DOING.</p>
  49. <p begin="00:01:45.57" end="00:01:47.57" region="speaker"><metadata ccrow="14" cccol="1"/>SHE&apos;S STEP BY STEP FULFILLING</p>
  50. <p begin="00:01:47.57" end="00:01:50.87" region="speaker"><metadata ccrow="14" cccol="0"/>HER DESTINY AND MY JOB IS TO GET</p>
  51. <p begin="00:01:50.87" end="00:01:52.50" region="speaker"><metadata ccrow="14" cccol="1"/>OUT OF THE WAY AND TRY TO KEEP</p>
  52. <p begin="00:01:52.50" end="00:01:58.37" region="speaker"><metadata ccrow="14" cccol="12"/>MY JOB.</p>
  53. <p begin="00:01:58.37" end="00:02:02.73" region="speaker"><metadata ccrow="14" cccol="10"/>DR. CORBETT.</p>
  54. <p begin="00:02:02.73" end="00:02:04.87" region="speaker"><metadata ccrow="14" cccol="3"/>&gt;&gt; THANK YOU, DR. GRAHAM.</p>
  55. <p begin="00:02:04.87" end="00:02:05.30" region="speaker"><metadata ccrow="14" cccol="9"/>HI, EVERYONE.</p>
  56. <p begin="00:02:05.30" end="00:02:06.90" region="speaker"><metadata ccrow="14" cccol="2"/>IT IS A PLEASURE TO BE HERE</p>
  57. <p begin="00:02:06.90" end="00:02:09.70" region="speaker"><metadata ccrow="14" cccol="0"/>TODAY TO TALK TO YOU ABOUT SOME</p>
  58. <p begin="00:02:09.70" end="00:02:11.80" region="speaker"><metadata ccrow="14" cccol="1"/>OF THE WORK THAT WE DO IN THE</p>
  59. <p begin="00:02:11.80" end="00:02:16.43" region="speaker"><metadata ccrow="14" cccol="4"/>VACCINE RESEARCH CENTER.</p>
  60. <p begin="00:02:16.43" end="00:02:18.70" region="speaker"><metadata ccrow="14" cccol="2"/>OVERALL THE IDEA IS THAT WE</p>
  61. <p begin="00:02:18.70" end="00:02:20.03" region="speaker"><metadata ccrow="14" cccol="2"/>CREATE VACCINE ANTIGENS AND</p>
  62. <p begin="00:02:20.03" end="00:02:21.87" region="speaker"><metadata ccrow="14" cccol="3"/>STUDY THEM IN SMALL ANIMAL</p>
  63. <p begin="00:02:21.87" end="00:02:22.83" region="speaker"><metadata ccrow="14" cccol="4"/>MODELS WITH THE IDEA OF</p>
  64. <p begin="00:02:22.83" end="00:02:25.17" region="speaker"><metadata ccrow="14" cccol="4"/>PROGRESSING THEM INTO A</p>
  65. <p begin="00:02:25.17" end="00:02:26.90" region="speaker"><metadata ccrow="14" cccol="2"/>PRE-CLINICAL TRIALS AND ALSO</p>
  66. <p begin="00:02:26.90" end="00:02:31.83" region="speaker"><metadata ccrow="14" cccol="1"/>INTO PHASE 1 CLINICAL TRIALS.</p>
  67. <p begin="00:02:31.83" end="00:02:33.60" region="speaker"><metadata ccrow="14" cccol="2"/>I&apos;M A RESEARCH FELLOW UNDER</p>
  68. <p begin="00:02:33.60" end="00:02:37.17" region="speaker"><metadata ccrow="14" cccol="2"/>DR. GRAHAM BUT I AM ALSO THE</p>
  69. <p begin="00:02:37.17" end="00:02:38.80" region="speaker"><metadata ccrow="14" cccol="1"/>SCIENTIFIC LEAD OF THE CORONA</p>
  70. <p begin="00:02:38.80" end="00:02:40.43" region="speaker"><metadata ccrow="14" cccol="1"/>VIRUS WHO ARE A LOT OF PEOPLE</p>
  71. <p begin="00:02:40.43" end="00:02:42.63" region="speaker"><metadata ccrow="14" cccol="1"/>SITTING HERE IN THE MIDDLE OF</p>
  72. <p begin="00:02:42.63" end="00:02:45.33" region="speaker"><metadata ccrow="14" cccol="6"/>THIS, AMPHITHEATER.</p>
  73. <p begin="00:02:45.33" end="00:02:46.90" region="speaker"><metadata ccrow="14" cccol="3"/>WE ARE REALLY STARTING TO</p>
  74. <p begin="00:02:46.90" end="00:02:49.93" region="speaker"><metadata ccrow="14" cccol="2"/>UNDERSTAND A LOT ABOUT MERS</p>
  75. <p begin="00:02:49.93" end="00:02:52.17" region="speaker"><metadata ccrow="14" cccol="0"/>CORONA VIRUS AND ANTIBODIES E LE</p>
  76. <p begin="00:02:52.17" end="00:02:54.57" region="speaker"><metadata ccrow="14" cccol="1"/>SITED BY -- ELICITED BY SMALL</p>
  77. <p begin="00:02:54.57" end="00:02:57.93" region="speaker"><metadata ccrow="14" cccol="1"/>ANIMAL MODELS WHO GET VACCINES</p>
  78. <p begin="00:02:57.93" end="00:02:59.77" region="speaker"><metadata ccrow="14" cccol="0"/>SUCH AS OURS AND TRYING TO DELVE</p>
  79. <p begin="00:02:59.77" end="00:03:03.13" region="speaker"><metadata ccrow="14" cccol="0"/>HOW TO ELICIT ANTIBODY RESPONSES</p>
  80. <p begin="00:03:03.13" end="00:03:05.53" region="speaker"><metadata ccrow="14" cccol="3"/>TO MULTIPLE SITES OF VERY</p>
  81. <p begin="00:03:05.53" end="00:03:09.67" region="speaker"><metadata ccrow="14" cccol="10"/>NEARIBILITY.</p>
  82. <p begin="00:03:09.67" end="00:03:11.47" region="speaker"><metadata ccrow="14" cccol="6"/>SO -- VULNERABILITY.</p>
  83. <p begin="00:03:11.47" end="00:03:13.80" region="speaker"><metadata ccrow="14" cccol="1"/>IT IS LARGE FAMILY OF VIRUSES</p>
  84. <p begin="00:03:13.80" end="00:03:15.50" region="speaker"><metadata ccrow="14" cccol="1"/>THAT GENERALLY DWELL IN ANIMAL</p>
  85. <p begin="00:03:15.50" end="00:03:15.87" region="speaker"><metadata ccrow="14" cccol="10"/>RESERVOIRS.</p>
  86. <p begin="00:03:15.87" end="00:03:17.07" region="speaker"><metadata ccrow="14" cccol="1"/>SO YOU CAN SEE HERE THAT THERE</p>
  87. <p begin="00:03:17.07" end="00:03:19.77" region="speaker"><metadata ccrow="14" cccol="2"/>ARE BETA CORONA VIRUS, ALPHA</p>
  88. <p begin="00:03:19.77" end="00:03:21.97" region="speaker"><metadata ccrow="14" cccol="2"/>CORONA VIRUSES, GAMMA CORONA</p>
  89. <p begin="00:03:21.97" end="00:03:25.67" region="speaker"><metadata ccrow="14" cccol="0"/>VIRUSES AND A LOT ACTUALLY LIVE</p>
  90. <p begin="00:03:25.67" end="00:03:29.03" region="speaker"><metadata ccrow="14" cccol="3"/>IN BATS OR OTHER ANIMALS.</p>
  91. <p begin="00:03:29.03" end="00:03:31.57" region="speaker"><metadata ccrow="14" cccol="1"/>THERE ARE THOUGH SOME ENDEMIC</p>
  92. <p begin="00:03:31.57" end="00:03:33.47" region="speaker"><metadata ccrow="14" cccol="3"/>CORONA VIRUSES THAT INFECT</p>
  93. <p begin="00:03:33.47" end="00:03:37.80" region="speaker"><metadata ccrow="14" cccol="0"/>HUMANS AND CAUSE 30% OF THE COLD</p>
  94. <p begin="00:03:37.80" end="00:03:39.50" region="speaker"><metadata ccrow="14" cccol="0"/>AND FLU LIKE SYMPTOMS DURING FLU</p>
  95. <p begin="00:03:39.50" end="00:03:42.97" region="speaker"><metadata ccrow="14" cccol="2"/>SEASON, THESE ARE THE HK 1s,</p>
  96. <p begin="00:03:42.97" end="00:03:46.70" region="speaker"><metadata ccrow="14" cccol="4"/>CO 43s, 229E AND ML 63.</p>
  97. <p begin="00:03:46.70" end="00:03:47.90" region="speaker"><metadata ccrow="14" cccol="3"/>THEN THERE ARE A COUPLE OF</p>
  98. <p begin="00:03:47.90" end="00:03:50.00" region="speaker"><metadata ccrow="14" cccol="1"/>CORONA VIRUSES YOU HEARD OF IN</p>
  99. <p begin="00:03:50.00" end="00:03:53.70" region="speaker"><metadata ccrow="14" cccol="0"/>THE NEWS WHICH ARE THE ONES THAT</p>
  100. <p begin="00:03:53.70" end="00:03:56.30" region="speaker"><metadata ccrow="14" cccol="2"/>ARE RUNNING RAMPANT IN SWINE</p>
  101. <p begin="00:03:56.30" end="00:03:58.90" region="speaker"><metadata ccrow="14" cccol="0"/>FARMS AROUND THE WORLD, THE FOR</p>
  102. <p begin="00:03:58.90" end="00:03:59.73" region="speaker"><metadata ccrow="14" cccol="6"/>SEEN CORONA VIRUSES.</p>
  103. <p begin="00:03:59.73" end="00:04:00.80" region="speaker"><metadata ccrow="14" cccol="1"/>AT THE NATIONAL INSTITUTES OF</p>
  104. <p begin="00:04:00.80" end="00:04:03.47" region="speaker"><metadata ccrow="14" cccol="4"/>HEALTH WE STUDY VIRUSES</p>
  105. <p begin="00:04:03.47" end="00:04:04.20" region="speaker"><metadata ccrow="14" cccol="1"/>IMPORTANT TOWARDS HUMAN HEALTH</p>
  106. <p begin="00:04:04.20" end="00:04:06.30" region="speaker"><metadata ccrow="14" cccol="0"/>THERE ARE SOME VIRUSES LIKE PEDB</p>
  107. <p begin="00:04:06.30" end="00:04:10.00" region="speaker"><metadata ccrow="14" cccol="2"/>THAT ARE CORONA VIRUSES THAT</p>
  108. <p begin="00:04:10.00" end="00:04:11.07" region="speaker"><metadata ccrow="14" cccol="2"/>ALSO HAVE AN OPPORTUNITY FOR</p>
  109. <p begin="00:04:11.07" end="00:04:12.47" region="speaker"><metadata ccrow="14" cccol="1"/>VACCINE DEVELOPMENT AS I START</p>
  110. <p begin="00:04:12.47" end="00:04:14.63" region="speaker"><metadata ccrow="14" cccol="0"/>TO THINK ABOUT WHAT WE CONSIDER</p>
  111. <p begin="00:04:14.63" end="00:04:17.33" region="speaker"><metadata ccrow="14" cccol="4"/>TO BE UNIVERSAL VACCINE</p>
  112. <p begin="00:04:17.33" end="00:04:18.13" region="speaker"><metadata ccrow="14" cccol="11"/>STRATEGY.</p>
  113. <p begin="00:04:18.13" end="00:04:20.17" region="speaker"><metadata ccrow="14" cccol="2"/>THEN THERE ARE THE BIG ONES.</p>
  114. <p begin="00:04:20.17" end="00:04:24.17" region="speaker"><metadata ccrow="14" cccol="3"/>THE SARS WHICH IN 2004 RAN</p>
  115. <p begin="00:04:24.17" end="00:04:26.50" region="speaker"><metadata ccrow="14" cccol="0"/>ACROSS THIS WORLD, CAUSED ABOUT</p>
  116. <p begin="00:04:26.50" end="00:04:28.70" region="speaker"><metadata ccrow="14" cccol="2"/>800 DEATHS IN 32 COUNTRIES.</p>
  117. <p begin="00:04:28.70" end="00:04:31.50" region="speaker"><metadata ccrow="14" cccol="1"/>THEN IF YOU REMEMBER IN 2014,</p>
  118. <p begin="00:04:31.50" end="00:04:33.30" region="speaker"><metadata ccrow="14" cccol="2"/>THERE WAS THE MIDDLE EASTERN</p>
  119. <p begin="00:04:33.30" end="00:04:35.00" region="speaker"><metadata ccrow="14" cccol="2"/>RESPIRATORY SYNDROME VIRUS,</p>
  120. <p begin="00:04:35.00" end="00:04:38.00" region="speaker"><metadata ccrow="14" cccol="4"/>WHICH IS STILL ACTUALLY</p>
  121. <p begin="00:04:38.00" end="00:04:40.20" region="speaker"><metadata ccrow="14" cccol="1"/>INFECTING SOME PEOPLE IN SAUDI</p>
  122. <p begin="00:04:40.20" end="00:04:42.60" region="speaker"><metadata ccrow="14" cccol="0"/>ARABIA BUT LAST MAY WHEN I FIRST</p>
  123. <p begin="00:04:42.60" end="00:04:46.00" region="speaker"><metadata ccrow="14" cccol="0"/>MADE THIS SLIDE THERE WERE ABOUT</p>
  124. <p begin="00:04:46.00" end="00:04:48.77" region="speaker"><metadata ccrow="14" cccol="1"/>782 DEATHS FROM CORONA VIRUS.</p>
  125. <p begin="00:04:48.77" end="00:04:52.83" region="speaker"><metadata ccrow="14" cccol="1"/>SINCE THEN WE ADDED 100 CASES</p>
  126. <p begin="00:04:52.83" end="00:04:55.90" region="speaker"><metadata ccrow="14" cccol="2"/>THE LAST YEAR AND THERE&apos;S A</p>
  127. <p begin="00:04:55.90" end="00:04:56.80" region="speaker"><metadata ccrow="14" cccol="1"/>STEADY STATE MAN FETES STATION</p>
  128. <p begin="00:04:56.80" end="00:04:59.13" region="speaker"><metadata ccrow="14" cccol="1"/>OF THIS VIRUS IN SAUDI ARABIA.</p>
  129. <p begin="00:04:59.13" end="00:05:00.90" region="speaker"><metadata ccrow="14" cccol="4"/>SO THAT POSES A RISK FOR</p>
  130. <p begin="00:05:00.90" end="00:05:02.10" region="speaker"><metadata ccrow="14" cccol="1"/>PANDEMICS ACROSS THE GLOBE AND</p>
  131. <p begin="00:05:02.10" end="00:05:04.93" region="speaker"><metadata ccrow="14" cccol="2"/>IN ADDITION TO THE FACT THAT</p>
  132. <p begin="00:05:04.93" end="00:05:07.90" region="speaker"><metadata ccrow="14" cccol="0"/>THERE IS A GROUP AT UNC LAB THAT</p>
  133. <p begin="00:05:07.90" end="00:05:09.20" region="speaker"><metadata ccrow="14" cccol="1"/>SAYS THERE ARE CORONA VIRUSES</p>
  134. <p begin="00:05:09.20" end="00:05:11.50" region="speaker"><metadata ccrow="14" cccol="0"/>THAT LIVE IN BAT CAVES ALL OVER</p>
  135. <p begin="00:05:11.50" end="00:05:14.30" region="speaker"><metadata ccrow="14" cccol="2"/>THIS WORLD AND ARE POSED FOR</p>
  136. <p begin="00:05:14.30" end="00:05:15.53" region="speaker"><metadata ccrow="14" cccol="7"/>HUMAN EMERGENCE.&amp;</p>
  137. <p begin="00:05:15.53" end="00:05:17.93" region="speaker"><metadata ccrow="14" cccol="0"/>WHAT THAT MEANS IS ANY POINT WE</p>
  138. <p begin="00:05:17.93" end="00:05:19.63" region="speaker"><metadata ccrow="14" cccol="3"/>MAY GET INFECTD WITH A NEW</p>
  139. <p begin="00:05:19.63" end="00:05:20.83" region="speaker"><metadata ccrow="14" cccol="1"/>CORONA VIRUS THAT WILL CAUSE A</p>
  140. <p begin="00:05:20.83" end="00:05:22.50" region="speaker"><metadata ccrow="14" cccol="11"/>PANDEMIC.</p>
  141. <p begin="00:05:22.50" end="00:05:24.40" region="speaker"><metadata ccrow="14" cccol="3"/>FROM OUR PERSPECTIVE AS A</p>
  142. <p begin="00:05:24.40" end="00:05:25.97" region="speaker"><metadata ccrow="14" cccol="0"/>VACCINE RESEARCH CENTER WE WANT</p>
  143. <p begin="00:05:25.97" end="00:05:29.37" region="speaker"><metadata ccrow="14" cccol="1"/>TO CREATE A UNIVERSAL VACCINE</p>
  144. <p begin="00:05:29.37" end="00:05:33.90" region="speaker"><metadata ccrow="14" cccol="2"/>STRATEGY FOR CORONA VIRUSES.</p>
  145. <p begin="00:05:33.90" end="00:05:34.67" region="speaker"><metadata ccrow="14" cccol="6"/>WHAT DOES THAT MEAN?</p>
  146. <p begin="00:05:34.67" end="00:05:36.30" region="speaker"><metadata ccrow="14" cccol="1"/>I WORK IN FLU I GET ASKED THAT</p>
  147. <p begin="00:05:36.30" end="00:05:38.17" region="speaker"><metadata ccrow="14" cccol="2"/>QUESTION A LOT SO WE HAD TO</p>
  148. <p begin="00:05:38.17" end="00:05:41.30" region="speaker"><metadata ccrow="14" cccol="2"/>THINK ABOUT IT IN A SOFT AND</p>
  149. <p begin="00:05:41.30" end="00:05:42.20" region="speaker"><metadata ccrow="14" cccol="0"/>POLITICALLY CORRECT WAY BUT THE</p>
  150. <p begin="00:05:42.20" end="00:05:44.67" region="speaker"><metadata ccrow="14" cccol="0"/>WAY WE LIKE TO THINK ABOUT IT IS</p>
  151. <p begin="00:05:44.67" end="00:05:46.07" region="speaker"><metadata ccrow="14" cccol="4"/>THAT A UNIVERSAL VACCINE</p>
  152. <p begin="00:05:46.07" end="00:05:47.77" region="speaker"><metadata ccrow="14" cccol="1"/>SOLUTION IS SOMETHING THAT IS</p>
  153. <p begin="00:05:47.77" end="00:05:49.57" region="speaker"><metadata ccrow="14" cccol="3"/>FAST SO THAT IS A VACCINE</p>
  154. <p begin="00:05:49.57" end="00:05:51.30" region="speaker"><metadata ccrow="14" cccol="0"/>TECHNOLOGY THAT CAN BE PRODUCED</p>
  155. <p begin="00:05:51.30" end="00:05:54.03" region="speaker"><metadata ccrow="14" cccol="2"/>IN VAST QUANTITIES QUICKLY.</p>
  156. <p begin="00:05:54.03" end="00:05:55.87" region="speaker"><metadata ccrow="14" cccol="2"/>SOMETHING THAT IS RELIABLE.</p>
  157. <p begin="00:05:55.87" end="00:05:59.47" region="speaker"><metadata ccrow="14" cccol="6"/>IT UPHOLDS RELIABLE</p>
  158. <p begin="00:05:59.47" end="00:06:00.17" region="speaker"><metadata ccrow="14" cccol="1"/>MANUFACTURABILITY STANDARD AND</p>
  159. <p begin="00:06:00.17" end="00:06:01.97" region="speaker"><metadata ccrow="14" cccol="8"/>THEN UNIVERSAL.</p>
  160. <p begin="00:06:01.97" end="00:06:03.70" region="speaker"><metadata ccrow="14" cccol="3"/>VACCINE TECHNOLOGY THAT IS</p>
  161. <p begin="00:06:03.70" end="00:06:06.07" region="speaker"><metadata ccrow="14" cccol="2"/>PREMIUMTIVE AND PROVIDES --</p>
  162. <p begin="00:06:06.07" end="00:06:07.77" region="speaker"><metadata ccrow="14" cccol="4"/>PREEMPTIVE AND PROVIDES</p>
  163. <p begin="00:06:07.77" end="00:06:09.10" region="speaker"><metadata ccrow="14" cccol="3"/>PROTECTION AGAINST FUTURE</p>
  164. <p begin="00:06:09.10" end="00:06:10.10" region="speaker"><metadata ccrow="14" cccol="11"/>OUTBREAKS.</p>
  165. <p begin="00:06:10.10" end="00:06:11.60" region="speaker"><metadata ccrow="14" cccol="0"/>THE STRATEGY FOR THIS THE WAS TO</p>
  166. <p begin="00:06:11.60" end="00:06:13.40" region="speaker"><metadata ccrow="14" cccol="1"/>LOOK AT THE CORONA VIRUS SPIKE</p>
  167. <p begin="00:06:13.40" end="00:06:13.63" region="speaker"><metadata ccrow="14" cccol="12"/>PROTEIN.</p>
  168. <p begin="00:06:13.63" end="00:06:14.60" region="speaker"><metadata ccrow="14" cccol="1"/>THIS IS PROTEIN ON THE SURFACE</p>
  169. <p begin="00:06:14.60" end="00:06:18.60" region="speaker"><metadata ccrow="14" cccol="0"/>OF O THE VIRAL MEMBRANE, AND IT</p>
  170. <p begin="00:06:18.60" end="00:06:20.30" region="speaker"><metadata ccrow="14" cccol="1"/>CAUSES ATTACHMENT INFUSION TO</p>
  171. <p begin="00:06:20.30" end="00:06:23.10" region="speaker"><metadata ccrow="14" cccol="0"/>THE HOST CELL RECEPTOR WHICH FOR</p>
  172. <p begin="00:06:23.10" end="00:06:25.60" region="speaker"><metadata ccrow="14" cccol="2"/>MERS IS THE DPP 4 RECEPTOR.</p>
  173. <p begin="00:06:25.60" end="00:06:28.47" region="speaker"><metadata ccrow="14" cccol="0"/>IT IS FOR THAT REASON THE TARGET</p>
  174. <p begin="00:06:28.47" end="00:06:31.17" region="speaker"><metadata ccrow="14" cccol="0"/>PROTECTED ANTIBODIES AND PREFER</p>
  175. <p begin="00:06:31.17" end="00:06:31.93" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIGEN FOR VACCINE DEVELOPMENT.</p>
  176. <p begin="00:06:31.93" end="00:06:35.37" region="speaker"><metadata ccrow="14" cccol="0"/>SO THIS IS A SCHEMA OF THE THREE</p>
  177. <p begin="00:06:35.37" end="00:06:38.23" region="speaker"><metadata ccrow="14" cccol="0"/>HUMAN CORONA VIRUSES FIRSTLY HKU</p>
  178. <p begin="00:06:38.23" end="00:06:41.63" region="speaker"><metadata ccrow="14" cccol="1"/>1, SARS CORONA VIRUS AND MERS</p>
  179. <p begin="00:06:41.63" end="00:06:43.43" region="speaker"><metadata ccrow="14" cccol="0"/>CORONA VIRUS, THE THINGS TO DRAW</p>
  180. <p begin="00:06:43.43" end="00:06:46.27" region="speaker"><metadata ccrow="14" cccol="0"/>TO YOUR ATTENTION IS THAT THERE</p>
  181. <p begin="00:06:46.27" end="00:06:48.83" region="speaker"><metadata ccrow="14" cccol="1"/>ARE TWO PORTIONS OF THIS SPIKE</p>
  182. <p begin="00:06:48.83" end="00:06:50.27" region="speaker"><metadata ccrow="14" cccol="1"/>PROTEIN, FIRST HALF IS CALLED</p>
  183. <p begin="00:06:50.27" end="00:06:52.37" region="speaker"><metadata ccrow="14" cccol="2"/>THE S 1 REGION, THIS IS THAT</p>
  184. <p begin="00:06:52.37" end="00:06:53.60" region="speaker"><metadata ccrow="14" cccol="1"/>GLOBULAR HEAD REGION THAT SITS</p>
  185. <p begin="00:06:53.60" end="00:06:54.77" region="speaker"><metadata ccrow="14" cccol="1"/>AT THE TOP OF THE SECOND HALF</p>
  186. <p begin="00:06:54.77" end="00:06:56.37" region="speaker"><metadata ccrow="14" cccol="3"/>WHICH CONTAINS THE FUSION</p>
  187. <p begin="00:06:56.37" end="00:06:57.90" region="speaker"><metadata ccrow="14" cccol="1"/>MACHINERY AND THAT IS THE S 2</p>
  188. <p begin="00:06:57.90" end="00:06:59.43" region="speaker"><metadata ccrow="14" cccol="12"/>REGION.</p>
  189. <p begin="00:06:59.43" end="00:07:01.07" region="speaker"><metadata ccrow="14" cccol="2"/>AS YOU THINK PANT UNIVERSAL</p>
  190. <p begin="00:07:01.07" end="00:07:03.30" region="speaker"><metadata ccrow="14" cccol="0"/>VACCINE DEVELOPMENT THE IDEA IS</p>
  191. <p begin="00:07:03.30" end="00:07:06.53" region="speaker"><metadata ccrow="14" cccol="1"/>THAT YOU WILL TARGET EPITOPES</p>
  192. <p begin="00:07:06.53" end="00:07:09.50" region="speaker"><metadata ccrow="14" cccol="1"/>THAT ARE CONSERVED ACROSS MANY</p>
  193. <p begin="00:07:09.50" end="00:07:11.30" region="speaker"><metadata ccrow="14" cccol="6"/>OF THE VIRUS STRAIN.</p>
  194. <p begin="00:07:11.30" end="00:07:13.20" region="speaker"><metadata ccrow="14" cccol="1"/>WITH THAT THE IDEA BEHIND OUR</p>
  195. <p begin="00:07:13.20" end="00:07:15.70" region="speaker"><metadata ccrow="14" cccol="4"/>VACCINE TECHNOLOGY IS WE</p>
  196. <p begin="00:07:15.70" end="00:07:16.90" region="speaker"><metadata ccrow="14" cccol="2"/>ENCOMPASS THIS ENTIRE SPIKE</p>
  197. <p begin="00:07:16.90" end="00:07:18.30" region="speaker"><metadata ccrow="14" cccol="1"/>PROTEIN AND PARTICULARLY THINK</p>
  198. <p begin="00:07:18.30" end="00:07:19.60" region="speaker"><metadata ccrow="14" cccol="0"/>ABOUT THOSE EPITOPESES THAT ARE</p>
  199. <p begin="00:07:19.60" end="00:07:22.20" region="speaker"><metadata ccrow="14" cccol="0"/>OUTSIDE OF THE RECEPTOR BINDING</p>
  200. <p begin="00:07:22.20" end="00:07:24.60" region="speaker"><metadata ccrow="14" cccol="0"/>DOMAIN AND MORE CONSERVED ACROSS</p>
  201. <p begin="00:07:24.60" end="00:07:29.20" region="speaker"><metadata ccrow="14" cccol="5"/>THE DIFFERENT SPECIES.</p>
  202. <p begin="00:07:29.20" end="00:07:31.10" region="speaker"><metadata ccrow="14" cccol="5"/>SO MRS CORONA VACCINE</p>
  203. <p begin="00:07:31.10" end="00:07:32.23" region="speaker"><metadata ccrow="14" cccol="1"/>DEVELOPMENT WHERE ARE WE NOW?</p>
  204. <p begin="00:07:32.23" end="00:07:33.90" region="speaker"><metadata ccrow="14" cccol="1"/>I ALWAYS GET THIS QUESTION, I</p>
  205. <p begin="00:07:33.90" end="00:07:35.50" region="speaker"><metadata ccrow="14" cccol="4"/>PARTICULARLY LIKE TO NOT</p>
  206. <p begin="00:07:35.50" end="00:07:37.20" region="speaker"><metadata ccrow="14" cccol="0"/>NECESSARILY TALK ABOUT IT IN ANY</p>
  207. <p begin="00:07:37.20" end="00:07:38.00" region="speaker"><metadata ccrow="14" cccol="1"/>DEPTH BECAUSE THE TRUTH OF THE</p>
  208. <p begin="00:07:38.00" end="00:07:41.50" region="speaker"><metadata ccrow="14" cccol="3"/>MATTER IS THAT ACROSS ALL</p>
  209. <p begin="00:07:41.50" end="00:07:44.60" region="speaker"><metadata ccrow="14" cccol="1"/>RESEARCH LABS IN THIS WORLD WE</p>
  210. <p begin="00:07:44.60" end="00:07:46.10" region="speaker"><metadata ccrow="14" cccol="4"/>TESTED SEVERAL STAGES OF</p>
  211. <p begin="00:07:46.10" end="00:07:48.10" region="speaker"><metadata ccrow="14" cccol="1"/>VACCINES OR TYPES OF VACCINES</p>
  212. <p begin="00:07:48.10" end="00:07:50.73" region="speaker"><metadata ccrow="14" cccol="0"/>THROUGH THE PRE-CLINICAL STAGE.</p>
  213. <p begin="00:07:50.73" end="00:07:53.23" region="speaker"><metadata ccrow="14" cccol="0"/>THE OVER YARR. ING IDEA IS THAT</p>
  214. <p begin="00:07:53.23" end="00:07:56.03" region="speaker"><metadata ccrow="14" cccol="3"/>WE CAN CREATE SOME TYPE OF</p>
  215. <p begin="00:07:56.03" end="00:07:57.20" region="speaker"><metadata ccrow="14" cccol="7"/>HUMORAL IMMUNITY.</p>
  216. <p begin="00:07:57.20" end="00:07:59.53" region="speaker"><metadata ccrow="14" cccol="0"/>GENERALLY PRIMATES AND MICE ARE</p>
  217. <p begin="00:07:59.53" end="00:08:01.40" region="speaker"><metadata ccrow="14" cccol="2"/>PROTECTED WITH THESE VACCINE</p>
  218. <p begin="00:08:01.40" end="00:08:05.10" region="speaker"><metadata ccrow="14" cccol="1"/>CONTRA BUT I WANT TO JUST SAY</p>
  219. <p begin="00:08:05.10" end="00:08:07.03" region="speaker"><metadata ccrow="14" cccol="4"/>THAT EVEN AT THE VACCINE</p>
  220. <p begin="00:08:07.03" end="00:08:07.80" region="speaker"><metadata ccrow="14" cccol="4"/>RESEARCH CENTER WE HAD A</p>
  221. <p begin="00:08:07.80" end="00:08:09.77" region="speaker"><metadata ccrow="14" cccol="0"/>PROMISING VACCINE CANDIDATE THAT</p>
  222. <p begin="00:08:09.77" end="00:08:12.80" region="speaker"><metadata ccrow="14" cccol="1"/>WAS A DNA VACCINE PLATFORM THE</p>
  223. <p begin="00:08:12.80" end="00:08:14.10" region="speaker"><metadata ccrow="14" cccol="0"/>ONE THING MOST PEOPLE DON&apos;T TELL</p>
  224. <p begin="00:08:14.10" end="00:08:15.60" region="speaker"><metadata ccrow="14" cccol="2"/>YOU WHEN THEY PUBLISH THESE</p>
  225. <p begin="00:08:15.60" end="00:08:18.50" region="speaker"><metadata ccrow="14" cccol="1"/>VACCINE CANDIDATES IS THAT WE</p>
  226. <p begin="00:08:18.50" end="00:08:20.50" region="speaker"><metadata ccrow="14" cccol="4"/>ARE GENERALLY ELICITING</p>
  227. <p begin="00:08:20.50" end="00:08:22.47" region="speaker"><metadata ccrow="14" cccol="2"/>REACCEPTERTOR BINDING DOMAIN</p>
  228. <p begin="00:08:22.47" end="00:08:25.20" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODY, ANTIBODIES SPECIFIC TO</p>
  229. <p begin="00:08:25.20" end="00:08:28.27" region="speaker"><metadata ccrow="14" cccol="1"/>THE VERY -- THE NON-CONSERVED</p>
  230. <p begin="00:08:28.27" end="00:08:32.80" region="speaker"><metadata ccrow="14" cccol="2"/>REGION THAT BINDS TO DPP 4.</p>
  231. <p begin="00:08:32.80" end="00:08:34.70" region="speaker"><metadata ccrow="14" cccol="2"/>SO OUR VACCINE CONSTRUCT WE</p>
  232. <p begin="00:08:34.70" end="00:08:37.47" region="speaker"><metadata ccrow="14" cccol="0"/>ACTUALLY TESTED LOTS OF VACCINES</p>
  233. <p begin="00:08:37.47" end="00:08:40.00" region="speaker"><metadata ccrow="14" cccol="2"/>EVEN -- I&apos;M SORRY, INCLUDING</p>
  234. <p begin="00:08:40.00" end="00:08:42.37" region="speaker"><metadata ccrow="14" cccol="0"/>DNA, A DNA CRIME WITH A PROTEIN</p>
  235. <p begin="00:08:42.37" end="00:08:43.97" region="speaker"><metadata ccrow="14" cccol="4"/>BOOST, THEN I DRAW YOUR</p>
  236. <p begin="00:08:43.97" end="00:08:45.17" region="speaker"><metadata ccrow="14" cccol="1"/>ATTENTION HERE TO THIS PART OF</p>
  237. <p begin="00:08:45.17" end="00:08:46.87" region="speaker"><metadata ccrow="14" cccol="3"/>THE GRAPH WHERE WE TESTED</p>
  238. <p begin="00:08:46.87" end="00:08:48.87" region="speaker"><metadata ccrow="14" cccol="1"/>PROTEIN VACCINATIONS AS WELL.</p>
  239. <p begin="00:08:48.87" end="00:08:50.87" region="speaker"><metadata ccrow="14" cccol="1"/>SO WHAT&apos;S IMPORTANT TO NOTE IS</p>
  240. <p begin="00:08:50.87" end="00:08:53.20" region="speaker"><metadata ccrow="14" cccol="0"/>THAT SOME OF OUR LEADING PROTEIN</p>
  241. <p begin="00:08:53.20" end="00:08:55.70" region="speaker"><metadata ccrow="14" cccol="2"/>VACCINE CANDIDATES WERE S 1</p>
  242. <p begin="00:08:55.70" end="00:08:58.27" region="speaker"><metadata ccrow="14" cccol="2"/>MONOMERIC PROTEIN, THIS IS A</p>
  243. <p begin="00:08:58.27" end="00:09:00.40" region="speaker"><metadata ccrow="14" cccol="0"/>SINGLE MONOMER OF THE S 1 REGION</p>
  244. <p begin="00:09:00.40" end="00:09:03.13" region="speaker"><metadata ccrow="14" cccol="1"/>OF THE SPIKE PROTEIN FROM MRS</p>
  245. <p begin="00:09:03.13" end="00:09:04.37" region="speaker"><metadata ccrow="14" cccol="9"/>CORONA VIRUS.</p>
  246. <p begin="00:09:04.37" end="00:09:06.43" region="speaker"><metadata ccrow="14" cccol="3"/>ALSO, A FULL LENGTH SPIKE</p>
  247. <p begin="00:09:06.43" end="00:09:09.03" region="speaker"><metadata ccrow="14" cccol="0"/>PROTEIN, HERE WE WERE UNABLE TO</p>
  248. <p begin="00:09:09.03" end="00:09:10.67" region="speaker"><metadata ccrow="14" cccol="2"/>MOVE THIS VACCINE CANDIDATE</p>
  249. <p begin="00:09:10.67" end="00:09:12.57" region="speaker"><metadata ccrow="14" cccol="3"/>FORWARD BECAUSE IT HAS LOW</p>
  250. <p begin="00:09:12.57" end="00:09:13.63" region="speaker"><metadata ccrow="14" cccol="3"/>EXPRESSION LEVELS AND WAS</p>
  251. <p begin="00:09:13.63" end="00:09:16.40" region="speaker"><metadata ccrow="14" cccol="4"/>HINDERED BY INSTABILITY.</p>
  252. <p begin="00:09:16.40" end="00:09:18.30" region="speaker"><metadata ccrow="14" cccol="3"/>SO AT THE VACCINE RESEARCH</p>
  253. <p begin="00:09:18.30" end="00:09:21.40" region="speaker"><metadata ccrow="14" cccol="2"/>CENTER WE HAVE GOTTEN REALLY</p>
  254. <p begin="00:09:21.40" end="00:09:23.00" region="speaker"><metadata ccrow="14" cccol="3"/>GOOD, I SHOULD SAY NOT WE,</p>
  255. <p begin="00:09:23.00" end="00:09:24.57" region="speaker"><metadata ccrow="14" cccol="0"/>PROTEIN ENGINEERS HAVE FOUGHTEN</p>
  256. <p begin="00:09:24.57" end="00:09:26.73" region="speaker"><metadata ccrow="14" cccol="0"/>REALLY GOOD AT STABILIZING THESE</p>
  257. <p begin="00:09:26.73" end="00:09:30.73" region="speaker"><metadata ccrow="14" cccol="1"/>CLASS 1 INFUSION PROTEINS AND</p>
  258. <p begin="00:09:30.73" end="00:09:31.97" region="speaker"><metadata ccrow="14" cccol="1"/>TESTING THEM FOR THEIR ABILITY</p>
  259. <p begin="00:09:31.97" end="00:09:36.67" region="speaker"><metadata ccrow="14" cccol="0"/>TO ELICIT IMMUNOGENIC ANTIBODIES</p>
  260. <p begin="00:09:36.67" end="00:09:38.47" region="speaker"><metadata ccrow="14" cccol="7"/>AND MOUSE MODELS.</p>
  261. <p begin="00:09:38.47" end="00:09:41.30" region="speaker"><metadata ccrow="14" cccol="0"/>SO THESE CLASS 1 FUSION PROTEINS</p>
  262. <p begin="00:09:41.30" end="00:09:43.17" region="speaker"><metadata ccrow="14" cccol="2"/>THAT ARE AKIN TO THE CORONA</p>
  263. <p begin="00:09:43.17" end="00:09:44.57" region="speaker"><metadata ccrow="14" cccol="0"/>VIRUS PROTEINS, ARE THINGS THAT</p>
  264. <p begin="00:09:44.57" end="00:09:46.57" region="speaker"><metadata ccrow="14" cccol="0"/>YOU PROBABLY HEARD OF MANY TIMES</p>
  265. <p begin="00:09:46.57" end="00:09:49.53" region="speaker"><metadata ccrow="14" cccol="1"/>BEFORE IN THE SEMINAR SUCH AS</p>
  266. <p begin="00:09:49.53" end="00:09:54.57" region="speaker"><metadata ccrow="14" cccol="2"/>THE FLUHA, HIV ENVELOPE, SO</p>
  267. <p begin="00:09:54.57" end="00:09:54.87" region="speaker"><metadata ccrow="14" cccol="13"/>FORTH.</p>
  268. <p begin="00:09:54.87" end="00:09:56.33" region="speaker"><metadata ccrow="14" cccol="1"/>THIS IS NOT BECAUSE DR. GRAHAM</p>
  269. <p begin="00:09:56.33" end="00:09:59.00" region="speaker"><metadata ccrow="14" cccol="3"/>IS SITTING IN THE OFFICE.</p>
  270. <p begin="00:09:59.00" end="00:10:00.20" region="speaker"><metadata ccrow="14" cccol="0"/>IN THE FRONT ROW BECAUSE I WANT</p>
  271. <p begin="00:10:00.20" end="00:10:03.27" region="speaker"><metadata ccrow="14" cccol="1"/>TO TAKE HIS OFFICE ONE DAY BUT</p>
  272. <p begin="00:10:03.27" end="00:10:06.00" region="speaker"><metadata ccrow="14" cccol="1"/>IT IS REALLY SHOW YOU THAT FOR</p>
  273. <p begin="00:10:06.00" end="00:10:07.20" region="speaker"><metadata ccrow="14" cccol="2"/>PARTICULARLY FOR OUR CF THE</p>
  274. <p begin="00:10:07.20" end="00:10:09.20" region="speaker"><metadata ccrow="14" cccol="5"/>FUSION PROTEIN FOR THE</p>
  275. <p begin="00:10:09.20" end="00:10:12.30" region="speaker"><metadata ccrow="14" cccol="0"/>RESPIRATORY SYNCYTIAL VIRUS, WE</p>
  276. <p begin="00:10:12.30" end="00:10:15.87" region="speaker"><metadata ccrow="14" cccol="1"/>HAVE STABILIZED ITS PROTEIN IN</p>
  277. <p begin="00:10:15.87" end="00:10:17.83" region="speaker"><metadata ccrow="14" cccol="1"/>TO THE PRE-FUSION CONFIRMATION</p>
  278. <p begin="00:10:17.83" end="00:10:19.37" region="speaker"><metadata ccrow="14" cccol="0"/>AND SHOWN THAT YOU CAN INCREASE</p>
  279. <p begin="00:10:19.37" end="00:10:23.27" region="speaker"><metadata ccrow="14" cccol="2"/>THE IMMUNOGENICITY BY ADDING</p>
  280. <p begin="00:10:23.27" end="00:10:24.77" region="speaker"><metadata ccrow="14" cccol="3"/>DISULFIDE BONDS AND CAVITY</p>
  281. <p begin="00:10:24.77" end="00:10:26.60" region="speaker"><metadata ccrow="14" cccol="3"/>FILLING MUTATIONS TO THIS</p>
  282. <p begin="00:10:26.60" end="00:10:26.87" region="speaker"><metadata ccrow="14" cccol="12"/>PROTEIN.</p>
  283. <p begin="00:10:26.87" end="00:10:28.70" region="speaker"><metadata ccrow="14" cccol="3"/>THIS TELLS US THIS TYPE OF</p>
  284. <p begin="00:10:28.70" end="00:10:30.57" region="speaker"><metadata ccrow="14" cccol="1"/>STRATEGY MAYBE USED FOR CORONA</p>
  285. <p begin="00:10:30.57" end="00:10:32.47" region="speaker"><metadata ccrow="14" cccol="2"/>VIRUSES TO EXPOSE SYSTEM OF</p>
  286. <p begin="00:10:32.47" end="00:10:34.17" region="speaker"><metadata ccrow="14" cccol="1"/>THOSE EPITOPES WE HAVEN&apos;T BEEN</p>
  287. <p begin="00:10:34.17" end="00:10:37.53" region="speaker"><metadata ccrow="14" cccol="0"/>SEEING WITH TRADITIONAL VACCINE</p>
  288. <p begin="00:10:37.53" end="00:10:38.00" region="speaker"><metadata ccrow="14" cccol="11"/>CONSTRUCT.</p>
  289. <p begin="00:10:38.00" end="00:10:39.20" region="speaker"><metadata ccrow="14" cccol="0"/>SO IT IS IMPORTANT TO NOTE THAT</p>
  290. <p begin="00:10:39.20" end="00:10:41.60" region="speaker"><metadata ccrow="14" cccol="2"/>THE RESPIRATORY -- SYNCYTIAL</p>
  291. <p begin="00:10:41.60" end="00:10:43.07" region="speaker"><metadata ccrow="14" cccol="1"/>VIRUS VACCINE CANDIDATE IS IN</p>
  292. <p begin="00:10:43.07" end="00:10:45.10" region="speaker"><metadata ccrow="14" cccol="0"/>CLINICAL TRIAL ACTUALLY IN THIS</p>
  293. <p begin="00:10:45.10" end="00:10:46.23" region="speaker"><metadata ccrow="14" cccol="0"/>BUILDING TEN RIGHT HERE IN THIS</p>
  294. <p begin="00:10:46.23" end="00:10:49.33" region="speaker"><metadata ccrow="14" cccol="12"/>CLINIC.</p>
  295. <p begin="00:10:49.33" end="00:10:51.93" region="speaker"><metadata ccrow="14" cccol="2"/>SO WHY DID WE REALLY WANT TO</p>
  296. <p begin="00:10:51.93" end="00:10:53.73" region="speaker"><metadata ccrow="14" cccol="3"/>ELICIT ANTIBODIES THAT ARE</p>
  297. <p begin="00:10:53.73" end="00:10:56.50" region="speaker"><metadata ccrow="14" cccol="2"/>OUTSIDE THE RECEPTOR BINDING</p>
  298. <p begin="00:10:56.50" end="00:10:57.60" region="speaker"><metadata ccrow="14" cccol="0"/>DOMAIN, THERE WERE PATHOGENS YOU</p>
  299. <p begin="00:10:57.60" end="00:10:59.60" region="speaker"><metadata ccrow="14" cccol="0"/>CAN ALIGN SEQUENCES AND YOU CAN</p>
  300. <p begin="00:10:59.60" end="00:11:01.77" region="speaker"><metadata ccrow="14" cccol="2"/>SEE OUTSIDE RECEPTOR BINDING</p>
  301. <p begin="00:11:01.77" end="00:11:03.67" region="speaker"><metadata ccrow="14" cccol="1"/>DOMAIN CONSERVED MOTIFS ACROSS</p>
  302. <p begin="00:11:03.67" end="00:11:04.83" region="speaker"><metadata ccrow="14" cccol="1"/>THE DIFFERENT SPECIESES IS OF</p>
  303. <p begin="00:11:04.83" end="00:11:07.17" region="speaker"><metadata ccrow="14" cccol="1"/>CORONA VIRUS BUT THEN WE HAVE</p>
  304. <p begin="00:11:07.17" end="00:11:07.67" region="speaker"><metadata ccrow="14" cccol="11"/>THE DATA.</p>
  305. <p begin="00:11:07.67" end="00:11:11.40" region="speaker"><metadata ccrow="14" cccol="0"/>SO LING SHU WITH THE REST OF MY</p>
  306. <p begin="00:11:11.40" end="00:11:13.50" region="speaker"><metadata ccrow="14" cccol="0"/>LAB RIGHT THERE ISOLATED A FULL</p>
  307. <p begin="00:11:13.50" end="00:11:16.53" region="speaker"><metadata ccrow="14" cccol="3"/>PANEL OF MRS CORONA VIRUS</p>
  308. <p begin="00:11:16.53" end="00:11:17.83" region="speaker"><metadata ccrow="14" cccol="5"/>MONOCLONAL ANTIBODIES.</p>
  309. <p begin="00:11:17.83" end="00:11:19.90" region="speaker"><metadata ccrow="14" cccol="1"/>WHAT SHE HAS SHOWN WITH THESE</p>
  310. <p begin="00:11:19.90" end="00:11:21.53" region="speaker"><metadata ccrow="14" cccol="2"/>ANTIBODIES IS THOUGH I DON&apos;T</p>
  311. <p begin="00:11:21.53" end="00:11:23.43" region="speaker"><metadata ccrow="14" cccol="3"/>SHOW SPECIFIC ONE IN THESE</p>
  312. <p begin="00:11:23.43" end="00:11:28.77" region="speaker"><metadata ccrow="14" cccol="1"/>PARTICULAR TABLES THE SPECIFIC</p>
  313. <p begin="00:11:28.77" end="00:11:32.40" region="speaker"><metadata ccrow="14" cccol="5"/>ANTIBODIES ELICIT ARE</p>
  314. <p begin="00:11:32.40" end="00:11:34.07" region="speaker"><metadata ccrow="14" cccol="1"/>UTILIZATION. WHEN YOU LOOK AT</p>
  315. <p begin="00:11:34.07" end="00:11:36.67" region="speaker"><metadata ccrow="14" cccol="4"/>COMPETITION ASSAYS WITH</p>
  316. <p begin="00:11:36.67" end="00:11:37.50" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODIES HAVE YOU FOUR UNIQUE</p>
  317. <p begin="00:11:37.50" end="00:11:39.97" region="speaker"><metadata ccrow="14" cccol="0"/>-- YOU HAVE FOUR UNIQUE CLASSES</p>
  318. <p begin="00:11:39.97" end="00:11:42.67" region="speaker"><metadata ccrow="14" cccol="1"/>OF RBD SPECIFIC ANTIBODIES AND</p>
  319. <p begin="00:11:42.67" end="00:11:45.07" region="speaker"><metadata ccrow="14" cccol="2"/>THREE UNIQUE CLASSES OF NTB</p>
  320. <p begin="00:11:45.07" end="00:11:47.27" region="speaker"><metadata ccrow="14" cccol="6"/>SPECIFIC ANTIBODIES.</p>
  321. <p begin="00:11:47.27" end="00:11:49.87" region="speaker"><metadata ccrow="14" cccol="3"/>WHAT THAT MEANS IS FOR THE</p>
  322. <p begin="00:11:49.87" end="00:11:52.00" region="speaker"><metadata ccrow="14" cccol="1"/>MONOCLONAL ANTIBODIES ISOLATED</p>
  323. <p begin="00:11:52.00" end="00:11:55.27" region="speaker"><metadata ccrow="14" cccol="3"/>FROM MRS SURVIVORS OR DNA</p>
  324. <p begin="00:11:55.27" end="00:11:57.27" region="speaker"><metadata ccrow="14" cccol="2"/>VACCINATED MICE AND MONKEYS,</p>
  325. <p begin="00:11:57.27" end="00:11:59.47" region="speaker"><metadata ccrow="14" cccol="1"/>THAT WE HAVE SEVEN CLASSES OF</p>
  326. <p begin="00:11:59.47" end="00:12:01.70" region="speaker"><metadata ccrow="14" cccol="2"/>ANTIBODIES THAT PARTICULARLY</p>
  327. <p begin="00:12:01.70" end="00:12:02.80" region="speaker"><metadata ccrow="14" cccol="5"/>TARGET FOR A VACCINE.</p>
  328. <p begin="00:12:02.80" end="00:12:05.50" region="speaker"><metadata ccrow="14" cccol="1"/>WHAT MADE IT EVEN MORE SPECIAL</p>
  329. <p begin="00:12:05.50" end="00:12:07.13" region="speaker"><metadata ccrow="14" cccol="2"/>WHEN WE START TOTTED LOOK AT</p>
  330. <p begin="00:12:07.13" end="00:12:08.53" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODIES AND THEIR MECHANISMS</p>
  331. <p begin="00:12:08.53" end="00:12:11.73" region="speaker"><metadata ccrow="14" cccol="0"/>FOR PROTECTION AND HOW WE MIGHT</p>
  332. <p begin="00:12:11.73" end="00:12:13.73" region="speaker"><metadata ccrow="14" cccol="4"/>MOVE FORWARD WITH THESE</p>
  333. <p begin="00:12:13.73" end="00:12:16.43" region="speaker"><metadata ccrow="14" cccol="2"/>ANTIBODIES IN THE EVENT OF A</p>
  334. <p begin="00:12:16.43" end="00:12:18.43" region="speaker"><metadata ccrow="14" cccol="0"/>PANDEMIC FOR MRS CORONA VIRUS IS</p>
  335. <p begin="00:12:18.43" end="00:12:19.93" region="speaker"><metadata ccrow="14" cccol="4"/>THAT WHEN YOU TEST THESE</p>
  336. <p begin="00:12:19.93" end="00:12:23.67" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODIES IN A PRNT ASSAY, I&apos;M</p>
  337. <p begin="00:12:23.67" end="00:12:25.80" region="speaker"><metadata ccrow="14" cccol="0"/>SORRY, WITH FOR STAIN MUTATIONS</p>
  338. <p begin="00:12:25.80" end="00:12:28.70" region="speaker"><metadata ccrow="14" cccol="2"/>WITH SIMPLE ISOLATES, IN BSL</p>
  339. <p begin="00:12:28.70" end="00:12:29.80" region="speaker"><metadata ccrow="14" cccol="0"/>LABORATORY VANDERBILT, WHAT YOU</p>
  340. <p begin="00:12:29.80" end="00:12:32.00" region="speaker"><metadata ccrow="14" cccol="1"/>CAN SEE IS THAT WHEN YOU TEST</p>
  341. <p begin="00:12:32.00" end="00:12:33.77" region="speaker"><metadata ccrow="14" cccol="2"/>WITH ONE MONOCLONAL ANTIBODY</p>
  342. <p begin="00:12:33.77" end="00:12:35.57" region="speaker"><metadata ccrow="14" cccol="1"/>SPECIFIC FOR RECEPTOR BINDING</p>
  343. <p begin="00:12:35.57" end="00:12:38.00" region="speaker"><metadata ccrow="14" cccol="2"/>DOMAIN REGION, YOU GET HIGH</p>
  344. <p begin="00:12:38.00" end="00:12:41.70" region="speaker"><metadata ccrow="14" cccol="3"/>LEVELS OF MUTATIONS UP TO</p>
  345. <p begin="00:12:41.70" end="00:12:42.10" region="speaker"><metadata ccrow="14" cccol="10"/>PASSAGE 10.</p>
  346. <p begin="00:12:42.10" end="00:12:43.33" region="speaker"><metadata ccrow="14" cccol="4"/>BUT WHEN YOU ADD TO THAT</p>
  347. <p begin="00:12:43.33" end="00:12:46.57" region="speaker"><metadata ccrow="14" cccol="0"/>RECEPTOR BINDING DOMAIN ANTIBODY</p>
  348. <p begin="00:12:46.57" end="00:12:48.97" region="speaker"><metadata ccrow="14" cccol="3"/>NTD SPECIFIC ANTIBODY YOU</p>
  349. <p begin="00:12:48.97" end="00:12:50.70" region="speaker"><metadata ccrow="14" cccol="0"/>ESSENTIALLY CHOP DOWN OCCURRENCE</p>
  350. <p begin="00:12:50.70" end="00:12:52.60" region="speaker"><metadata ccrow="14" cccol="1"/>OF MUTATIONS IN CELL CULTURE.</p>
  351. <p begin="00:12:52.60" end="00:12:55.07" region="speaker"><metadata ccrow="14" cccol="1"/>SO WHAT THAT IS SAYING IS THAT</p>
  352. <p begin="00:12:55.07" end="00:12:56.97" region="speaker"><metadata ccrow="14" cccol="0"/>COMBINATIONS OF THESE MONOCLONAL</p>
  353. <p begin="00:12:56.97" end="00:12:58.80" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODIES THAT TARGET DIFFERENT</p>
  354. <p begin="00:12:58.80" end="00:13:00.87" region="speaker"><metadata ccrow="14" cccol="2"/>DOMAINS ON THE SPIKE PROTEIN</p>
  355. <p begin="00:13:00.87" end="00:13:03.77" region="speaker"><metadata ccrow="14" cccol="1"/>DELAY VIRAL -- CAN DELAY VIRAL</p>
  356. <p begin="00:13:03.77" end="00:13:04.77" region="speaker"><metadata ccrow="14" cccol="12"/>ESCAPE.</p>
  357. <p begin="00:13:04.77" end="00:13:06.20" region="speaker"><metadata ccrow="14" cccol="0"/>ADDITIONALLY, WE SHOW THAT IN A</p>
  358. <p begin="00:13:06.20" end="00:13:10.67" region="speaker"><metadata ccrow="14" cccol="1"/>MOUSE MODEL, IN VITRO, IF YOU</p>
  359. <p begin="00:13:10.67" end="00:13:15.03" region="speaker"><metadata ccrow="14" cccol="0"/>GIVE RBD SPECIFIC ANTIBODY SITU</p>
  360. <p begin="00:13:15.03" end="00:13:18.17" region="speaker"><metadata ccrow="14" cccol="1"/>AND ADD G2 IN A COMBINED DOSE</p>
  361. <p begin="00:13:18.17" end="00:13:22.23" region="speaker"><metadata ccrow="14" cccol="0"/>YOU CAN DECREASE THE AMOUNTS OF</p>
  362. <p begin="00:13:22.23" end="00:13:25.63" region="speaker"><metadata ccrow="14" cccol="2"/>VIRAL LOAD FOUND IN LUCKS OF</p>
  363. <p begin="00:13:25.63" end="00:13:26.73" region="speaker"><metadata ccrow="14" cccol="10"/>THESE MICE.</p>
  364. <p begin="00:13:26.73" end="00:13:28.40" region="speaker"><metadata ccrow="14" cccol="4"/>WHETHER THE NTD SPECIFIC</p>
  365. <p begin="00:13:28.40" end="00:13:30.90" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODY ON TOP OF RBD SPECIFIC</p>
  366. <p begin="00:13:30.90" end="00:13:32.73" region="speaker"><metadata ccrow="14" cccol="2"/>ANTIBODY, YOU ARE PREVENTING</p>
  367. <p begin="00:13:32.73" end="00:13:34.37" region="speaker"><metadata ccrow="14" cccol="0"/>VIRAL ESCAPE IN THIS MOUSE MODEL</p>
  368. <p begin="00:13:34.37" end="00:13:36.63" region="speaker"><metadata ccrow="14" cccol="12"/>AS WELL.</p>
  369. <p begin="00:13:36.63" end="00:13:39.23" region="speaker"><metadata ccrow="14" cccol="1"/>SO WE HAVE ALL THOSE DATA, WE</p>
  370. <p begin="00:13:39.23" end="00:13:40.73" region="speaker"><metadata ccrow="14" cccol="1"/>HAVE THE MONOCLONAL ANTIBODIES</p>
  371. <p begin="00:13:40.73" end="00:13:42.23" region="speaker"><metadata ccrow="14" cccol="0"/>AND WE ARE ALLUDING TO THE FACT</p>
  372. <p begin="00:13:42.23" end="00:13:44.73" region="speaker"><metadata ccrow="14" cccol="3"/>THAT THE SPIKE PROTEIN IS</p>
  373. <p begin="00:13:44.73" end="00:13:47.00" region="speaker"><metadata ccrow="14" cccol="2"/>ESSENTIALLY A MIND FIELD OF</p>
  374. <p begin="00:13:47.00" end="00:13:47.97" region="speaker"><metadata ccrow="14" cccol="2"/>ANGIOGENIC TERRITORY WE CAN</p>
  375. <p begin="00:13:47.97" end="00:13:48.27" region="speaker"><metadata ccrow="14" cccol="12"/>EXPLORE.</p>
  376. <p begin="00:13:48.27" end="00:13:50.07" region="speaker"><metadata ccrow="14" cccol="3"/>WE JUST NEEDED THE TOOLS.</p>
  377. <p begin="00:13:50.07" end="00:13:56.33" region="speaker"><metadata ccrow="14" cccol="0"/>SO I CAME INTO THE LAB IN 2014.</p>
  378. <p begin="00:13:56.33" end="00:13:57.63" region="speaker"><metadata ccrow="14" cccol="2"/>AND REALLY STARTED TO THINK</p>
  379. <p begin="00:13:57.63" end="00:14:01.10" region="speaker"><metadata ccrow="14" cccol="0"/>ABOUT CORONA VIRUSES FROM ENDIME</p>
  380. <p begin="00:14:01.10" end="00:14:02.90" region="speaker"><metadata ccrow="14" cccol="0"/>PERSPECTIVE AND AT THAT TIME WE</p>
  381. <p begin="00:14:02.90" end="00:14:04.80" region="speaker"><metadata ccrow="14" cccol="3"/>WERE FOCUSING ON THE HUMAN</p>
  382. <p begin="00:14:04.80" end="00:14:07.90" region="speaker"><metadata ccrow="14" cccol="6"/>CORONA VIRUS HKU 1.</p>
  383. <p begin="00:14:07.90" end="00:14:10.73" region="speaker"><metadata ccrow="14" cccol="2"/>FORTUNATELY FOR US THE HKU 1</p>
  384. <p begin="00:14:10.73" end="00:14:12.60" region="speaker"><metadata ccrow="14" cccol="0"/>PROTEIN BEHAVE VERY WELL IN CELL</p>
  385. <p begin="00:14:12.60" end="00:14:14.00" region="speaker"><metadata ccrow="14" cccol="2"/>CULTURE AND WE WERE ABLE TO</p>
  386. <p begin="00:14:14.00" end="00:14:15.97" region="speaker"><metadata ccrow="14" cccol="1"/>PUBLISH THE FIRST HUMAN CORONA</p>
  387. <p begin="00:14:15.97" end="00:14:18.10" region="speaker"><metadata ccrow="14" cccol="5"/>VIRUS SPIKE STRUCTURE.</p>
  388. <p begin="00:14:18.10" end="00:14:21.37" region="speaker"><metadata ccrow="14" cccol="0"/>FOLLOWING THAT, PUBLICATION ARE</p>
  389. <p begin="00:14:21.37" end="00:14:22.60" region="speaker"><metadata ccrow="14" cccol="0"/>CROSS COUNTRY ON THE WEST COAST</p>
  390. <p begin="00:14:22.60" end="00:14:27.17" region="speaker"><metadata ccrow="14" cccol="0"/>UNIVERSITY OF WASHINGTON, DAVID</p>
  391. <p begin="00:14:27.17" end="00:14:27.77" region="speaker"><metadata ccrow="14" cccol="4"/>PUBLISHED ANOTHER SPIKE</p>
  392. <p begin="00:14:27.77" end="00:14:28.77" region="speaker"><metadata ccrow="14" cccol="2"/>STRUCTURE AND SINCE THEN THE</p>
  393. <p begin="00:14:28.77" end="00:14:31.07" region="speaker"><metadata ccrow="14" cccol="4"/>FIELD EXPLODED WITH THE</p>
  394. <p begin="00:14:31.07" end="00:14:32.77" region="speaker"><metadata ccrow="14" cccol="3"/>PUBLICATION OF THESE SPIKE</p>
  395. <p begin="00:14:32.77" end="00:14:34.30" region="speaker"><metadata ccrow="14" cccol="0"/>STRUCTURES FROM DIFFERENT CORONA</p>
  396. <p begin="00:14:34.30" end="00:14:34.60" region="speaker"><metadata ccrow="14" cccol="12"/>VIRUSES.</p>
  397. <p begin="00:14:34.60" end="00:14:37.00" region="speaker"><metadata ccrow="14" cccol="0"/>TODAY I&apos;M GOING TO FOCUS ON THE</p>
  398. <p begin="00:14:37.00" end="00:14:39.50" region="speaker"><metadata ccrow="14" cccol="3"/>MRS CORONA VIRUS STABILIZE</p>
  399. <p begin="00:14:39.50" end="00:14:40.80" region="speaker"><metadata ccrow="14" cccol="3"/>PRE-FUSION SPIKE WHICH WE</p>
  400. <p begin="00:14:40.80" end="00:14:44.40" region="speaker"><metadata ccrow="14" cccol="0"/>PUBLISH AROUND THE SAME TIME AS</p>
  401. <p begin="00:14:44.40" end="00:14:47.13" region="speaker"><metadata ccrow="14" cccol="4"/>GEORGE&apos;S GROUP IN CHINA.</p>
  402. <p begin="00:14:47.13" end="00:14:48.80" region="speaker"><metadata ccrow="14" cccol="4"/>REALLY TRY TO GET USE TO</p>
  403. <p begin="00:14:48.80" end="00:14:50.20" region="speaker"><metadata ccrow="14" cccol="0"/>UNDERSTAND WHAT WE ARE TRYING TO</p>
  404. <p begin="00:14:50.20" end="00:14:52.30" region="speaker"><metadata ccrow="14" cccol="2"/>DO IN REGARDS TO USING THIS</p>
  405. <p begin="00:14:52.30" end="00:14:53.63" region="speaker"><metadata ccrow="14" cccol="1"/>PARTICULAR TRIMER AS A VACCINE</p>
  406. <p begin="00:14:53.63" end="00:14:56.80" region="speaker"><metadata ccrow="14" cccol="12"/>ANTIGEN.</p>
  407. <p begin="00:14:56.80" end="00:15:00.57" region="speaker"><metadata ccrow="14" cccol="0"/>SO WE CALL THIS RATIONAL DESIGN</p>
  408. <p begin="00:15:00.57" end="00:15:02.40" region="speaker"><metadata ccrow="14" cccol="1"/>OF VACCINE ANTIGEN, THAT MEANS</p>
  409. <p begin="00:15:02.40" end="00:15:05.30" region="speaker"><metadata ccrow="14" cccol="3"/>YOU TAKE THE ATOMIC LEVEL</p>
  410. <p begin="00:15:05.30" end="00:15:07.40" region="speaker"><metadata ccrow="14" cccol="1"/>DETAILS OF SOME STRUCTURE YOU</p>
  411. <p begin="00:15:07.40" end="00:15:09.57" region="speaker"><metadata ccrow="14" cccol="0"/>KNOW SO IN THIS CASE IT WAS THE</p>
  412. <p begin="00:15:09.57" end="00:15:11.80" region="speaker"><metadata ccrow="14" cccol="0"/>HKU 1 STRUCTURE WE PUBLISHED IN</p>
  413. <p begin="00:15:11.80" end="00:15:13.80" region="speaker"><metadata ccrow="14" cccol="3"/>NATURE AND WE SCANNED THE</p>
  414. <p begin="00:15:13.80" end="00:15:15.20" region="speaker"><metadata ccrow="14" cccol="1"/>ENTIRETY OF THAT SPIKE PROTEIN</p>
  415. <p begin="00:15:15.20" end="00:15:18.40" region="speaker"><metadata ccrow="14" cccol="0"/>FOR MUTATIONS THAT WE CAN INSERT</p>
  416. <p begin="00:15:18.40" end="00:15:21.43" region="speaker"><metadata ccrow="14" cccol="6"/>INTO THE S 2 DOMAIN.</p>
  417. <p begin="00:15:21.43" end="00:15:24.07" region="speaker"><metadata ccrow="14" cccol="0"/>THOSE MUTATIONS WE ENDED UP WITH</p>
  418. <p begin="00:15:24.07" end="00:15:27.13" region="speaker"><metadata ccrow="14" cccol="3"/>AFTER TESTING HUNDREDS OF</p>
  419. <p begin="00:15:27.13" end="00:15:29.07" region="speaker"><metadata ccrow="14" cccol="0"/>MUTATIONS, WE ARE TWO MUTATIONS</p>
  420. <p begin="00:15:29.07" end="00:15:31.33" region="speaker"><metadata ccrow="14" cccol="1"/>FOR THE ENTIRETY OF THIS TALK</p>
  421. <p begin="00:15:31.33" end="00:15:33.17" region="speaker"><metadata ccrow="14" cccol="5"/>I&apos;LL CALL IT THE S 2P.</p>
  422. <p begin="00:15:33.17" end="00:15:35.77" region="speaker"><metadata ccrow="14" cccol="0"/>THIS PARTICULAR PROTEIN HAS TWO</p>
  423. <p begin="00:15:35.77" end="00:15:37.27" region="speaker"><metadata ccrow="14" cccol="2"/>PROLINES THAT SIT ON TOP OF</p>
  424. <p begin="00:15:37.27" end="00:15:39.97" region="speaker"><metadata ccrow="14" cccol="0"/>CENTRAL HELIX IN THE S-2 REGION</p>
  425. <p begin="00:15:39.97" end="00:15:42.63" region="speaker"><metadata ccrow="14" cccol="3"/>AND EFFECTIVELY THOSE TWO</p>
  426. <p begin="00:15:42.63" end="00:15:44.77" region="speaker"><metadata ccrow="14" cccol="4"/>PROLINE MUTATIONS TO THE</p>
  427. <p begin="00:15:44.77" end="00:15:46.57" region="speaker"><metadata ccrow="14" cccol="0"/>EXPRESSION OF THE SPIKE PROTEIN,</p>
  428. <p begin="00:15:46.57" end="00:15:49.67" region="speaker"><metadata ccrow="14" cccol="1"/>NOT JUST FOR MRS BUT FOR SARS,</p>
  429. <p begin="00:15:49.67" end="00:15:51.87" region="speaker"><metadata ccrow="14" cccol="1"/>YOU CAN SEE HERE WITH NEGATIVE</p>
  430. <p begin="00:15:51.87" end="00:15:55.73" region="speaker"><metadata ccrow="14" cccol="0"/>STAIN EM THAT THOSE TWO PROLINE</p>
  431. <p begin="00:15:55.73" end="00:15:58.13" region="speaker"><metadata ccrow="14" cccol="1"/>MUTATIONS AVOIDED -- PREVENTED</p>
  432. <p begin="00:15:58.13" end="00:16:00.77" region="speaker"><metadata ccrow="14" cccol="1"/>THE SPIKE PROTEIN FOR FLIPPING</p>
  433. <p begin="00:16:00.77" end="00:16:02.67" region="speaker"><metadata ccrow="14" cccol="2"/>UPON ITSELF FOR POST FUSION</p>
  434. <p begin="00:16:02.67" end="00:16:03.00" region="speaker"><metadata ccrow="14" cccol="9"/>CONFIRMATION.</p>
  435. <p begin="00:16:03.00" end="00:16:05.30" region="speaker"><metadata ccrow="14" cccol="1"/>THIS IS A PRE-FUSION STABILIZE</p>
  436. <p begin="00:16:05.30" end="00:16:06.10" region="speaker"><metadata ccrow="14" cccol="1"/>VERSION, THIS IS THE WILD TYPE</p>
  437. <p begin="00:16:06.10" end="00:16:07.30" region="speaker"><metadata ccrow="14" cccol="1"/>THAT YOU CAN SEE HAVE SOME OF</p>
  438. <p begin="00:16:07.30" end="00:16:12.93" region="speaker"><metadata ccrow="14" cccol="5"/>THE ELONGATED SHAPES.</p>
  439. <p begin="00:16:12.93" end="00:16:14.37" region="speaker"><metadata ccrow="14" cccol="1"/>INTERESTINGLY FOR US AND ALSO</p>
  440. <p begin="00:16:14.37" end="00:16:16.13" region="speaker"><metadata ccrow="14" cccol="1"/>FOR GEORGE GAL&apos;S GROUP IS THAT</p>
  441. <p begin="00:16:16.13" end="00:16:19.87" region="speaker"><metadata ccrow="14" cccol="1"/>NOT ONLY DO WE HAVE THE SPIKE</p>
  442. <p begin="00:16:19.87" end="00:16:20.73" region="speaker"><metadata ccrow="14" cccol="2"/>STRUCTURE BUT ONE THING THAT</p>
  443. <p begin="00:16:20.73" end="00:16:22.97" region="speaker"><metadata ccrow="14" cccol="1"/>BECAME APPARENT TO US IS THERE</p>
  444. <p begin="00:16:22.97" end="00:16:24.63" region="speaker"><metadata ccrow="14" cccol="2"/>WERE SOME SURFACES THAT WERE</p>
  445. <p begin="00:16:24.63" end="00:16:27.27" region="speaker"><metadata ccrow="14" cccol="1"/>PARTICULARLY UNEXPLORED AS WE</p>
  446. <p begin="00:16:27.27" end="00:16:28.80" region="speaker"><metadata ccrow="14" cccol="2"/>LOOK AT THE RECEPTOR BINDING</p>
  447. <p begin="00:16:28.80" end="00:16:30.57" region="speaker"><metadata ccrow="14" cccol="5"/>DOMAIN MOVEMENT HERE.</p>
  448. <p begin="00:16:30.57" end="00:16:32.80" region="speaker"><metadata ccrow="14" cccol="0"/>SO WHAT OUR STRUCTURE SHOWED IS</p>
  449. <p begin="00:16:32.80" end="00:16:35.67" region="speaker"><metadata ccrow="14" cccol="0"/>THAT THE SPIKE PROTEIN AT LEAST</p>
  450. <p begin="00:16:35.67" end="00:16:37.90" region="speaker"><metadata ccrow="14" cccol="0"/>THE EXO DOMAIN AS WE STUDIED IT</p>
  451. <p begin="00:16:37.90" end="00:16:40.47" region="speaker"><metadata ccrow="14" cccol="0"/>HAS FOUR POTENTIAL CONFIRMATIONS</p>
  452. <p begin="00:16:40.47" end="00:16:41.90" region="speaker"><metadata ccrow="14" cccol="0"/>WHEREBY RECEPTOR BINDING DOMAINS</p>
  453. <p begin="00:16:41.90" end="00:16:44.10" region="speaker"><metadata ccrow="14" cccol="1"/>ARE FLIPPED UPWARD OUTWARD OR</p>
  454. <p begin="00:16:44.10" end="00:16:45.83" region="speaker"><metadata ccrow="14" cccol="4"/>CLOSED IN ON EACH OTHER.</p>
  455. <p begin="00:16:45.83" end="00:16:49.30" region="speaker"><metadata ccrow="14" cccol="0"/>SO THAT WAS A REALLY INTERESTING</p>
  456. <p begin="00:16:49.30" end="00:16:50.47" region="speaker"><metadata ccrow="14" cccol="2"/>FINDING AND MADE US EXCITED</p>
  457. <p begin="00:16:50.47" end="00:16:51.77" region="speaker"><metadata ccrow="14" cccol="1"/>ABOUT EXPLORING ANTIBODIES TO</p>
  458. <p begin="00:16:51.77" end="00:16:53.33" region="speaker"><metadata ccrow="14" cccol="0"/>THE RECEPTOR BINDING DOMAIN AND</p>
  459. <p begin="00:16:53.33" end="00:16:56.00" region="speaker"><metadata ccrow="14" cccol="2"/>OUTSIDE THE RECEPTOR BINDING</p>
  460. <p begin="00:16:56.00" end="00:16:57.57" region="speaker"><metadata ccrow="14" cccol="12"/>DOMAIN.</p>
  461. <p begin="00:16:57.57" end="00:16:59.43" region="speaker"><metadata ccrow="14" cccol="1"/>FOR THE TWO P MUTATION INSIDE</p>
  462. <p begin="00:16:59.43" end="00:17:02.40" region="speaker"><metadata ccrow="14" cccol="3"/>THAT SPIKE PROTEIN, WE CAN</p>
  463. <p begin="00:17:02.40" end="00:17:03.97" region="speaker"><metadata ccrow="14" cccol="2"/>PRETTY MUCH DUMP THEM IN ANY</p>
  464. <p begin="00:17:03.97" end="00:17:06.13" region="speaker"><metadata ccrow="14" cccol="2"/>BACKBONE OF ANY BETA CORONA</p>
  465. <p begin="00:17:06.13" end="00:17:07.57" region="speaker"><metadata ccrow="14" cccol="2"/>VIRUS SPIKES AND EFFECTIVELY</p>
  466. <p begin="00:17:07.57" end="00:17:09.27" region="speaker"><metadata ccrow="14" cccol="4"/>STABILIZE THEM IN THEIR</p>
  467. <p begin="00:17:09.27" end="00:17:10.93" region="speaker"><metadata ccrow="14" cccol="0"/>PRE-FUSION CONFIRMATION AS WELL.</p>
  468. <p begin="00:17:10.93" end="00:17:12.90" region="speaker"><metadata ccrow="14" cccol="1"/>SO HERE IN THAT PAPER WITH THE</p>
  469. <p begin="00:17:12.90" end="00:17:15.80" region="speaker"><metadata ccrow="14" cccol="0"/>MRS SPIKE WE PUBLISHED HKU 1 SUP</p>
  470. <p begin="00:17:15.80" end="00:17:19.90" region="speaker"><metadata ccrow="14" cccol="0"/>AND SARS SUP AND SINCE THEN PUT</p>
  471. <p begin="00:17:19.90" end="00:17:24.43" region="speaker"><metadata ccrow="14" cccol="0"/>ANYONE THE BACKBONE OF 14 CORONA</p>
  472. <p begin="00:17:24.43" end="00:17:26.10" region="speaker"><metadata ccrow="14" cccol="3"/>VIRUS ECTO DOMAINS AT THIS</p>
  473. <p begin="00:17:26.10" end="00:17:28.20" region="speaker"><metadata ccrow="14" cccol="13"/>POINT.</p>
  474. <p begin="00:17:28.20" end="00:17:31.07" region="speaker"><metadata ccrow="14" cccol="2"/>INCLUDING THE ENDIME CORONA</p>
  475. <p begin="00:17:31.07" end="00:17:35.53" region="speaker"><metadata ccrow="14" cccol="3"/>VIRUSES SEEN HERE THAT ONE</p>
  476. <p begin="00:17:35.53" end="00:17:38.23" region="speaker"><metadata ccrow="14" cccol="0"/>PORCINE CORONA VIRUSES IMPORTANT</p>
  477. <p begin="00:17:38.23" end="00:17:40.33" region="speaker"><metadata ccrow="14" cccol="0"/>FOR FARMERS AROUND THE WORLD AND</p>
  478. <p begin="00:17:40.33" end="00:17:42.23" region="speaker"><metadata ccrow="14" cccol="4"/>POTENTIAL SPIKE PROTEIN</p>
  479. <p begin="00:17:42.23" end="00:17:44.33" region="speaker"><metadata ccrow="14" cccol="2"/>STABILIZED WITH TWO PROLINE</p>
  480. <p begin="00:17:44.33" end="00:17:45.03" region="speaker"><metadata ccrow="14" cccol="7"/>MUTATION AS WELL.</p>
  481. <p begin="00:17:45.03" end="00:17:46.90" region="speaker"><metadata ccrow="14" cccol="0"/>SO TO FUNCTIONALLY CHARACTERIZE</p>
  482. <p begin="00:17:46.90" end="00:17:51.63" region="speaker"><metadata ccrow="14" cccol="0"/>THIS MRS S 2P PROTEIN WE PUT THE</p>
  483. <p begin="00:17:51.63" end="00:17:55.53" region="speaker"><metadata ccrow="14" cccol="0"/>TWO MUTATIONS INTO THE BACKBONE</p>
  484. <p begin="00:17:55.53" end="00:17:58.53" region="speaker"><metadata ccrow="14" cccol="0"/>OF A PSEUDOVIRUS AND ASKED COULD</p>
  485. <p begin="00:17:58.53" end="00:17:59.93" region="speaker"><metadata ccrow="14" cccol="3"/>THE PSEUDOVIRUS EFFECT OR</p>
  486. <p begin="00:17:59.93" end="00:18:00.53" region="speaker"><metadata ccrow="14" cccol="8"/>TRANSDUCE CELLS.</p>
  487. <p begin="00:18:00.53" end="00:18:02.80" region="speaker"><metadata ccrow="14" cccol="0"/>WHAT YOU SEE HERE IS A GRAPH OF</p>
  488. <p begin="00:18:02.80" end="00:18:04.70" region="speaker"><metadata ccrow="14" cccol="0"/>THE -- OUR PSEUDOVIRUS WHICH IS</p>
  489. <p begin="00:18:04.70" end="00:18:07.30" region="speaker"><metadata ccrow="14" cccol="1"/>A LUCIFERASE BASED PSEUDOVIRUS</p>
  490. <p begin="00:18:07.30" end="00:18:08.97" region="speaker"><metadata ccrow="14" cccol="1"/>WHERE WE TRY TO INSPECT ON THE</p>
  491. <p begin="00:18:08.97" end="00:18:11.63" region="speaker"><metadata ccrow="14" cccol="0"/>SURFACE A TWO PROLINE SPIKE SEEN</p>
  492. <p begin="00:18:11.63" end="00:18:13.00" region="speaker"><metadata ccrow="14" cccol="3"/>IN RED OR WILD TYPE SPIKE.</p>
  493. <p begin="00:18:13.00" end="00:18:15.97" region="speaker"><metadata ccrow="14" cccol="0"/>YOU CAN SEE THAT THE TWO PROLIEN</p>
  494. <p begin="00:18:15.97" end="00:18:17.97" region="speaker"><metadata ccrow="14" cccol="4"/>RENDERS THAT PSEUDOVIRUS</p>
  495. <p begin="00:18:17.97" end="00:18:18.37" region="speaker"><metadata ccrow="14" cccol="8"/>NON-INFECTIOUS.</p>
  496. <p begin="00:18:18.37" end="00:18:20.47" region="speaker"><metadata ccrow="14" cccol="0"/>IF YOU EXPRESS THAT TWO PROLINE</p>
  497. <p begin="00:18:20.47" end="00:18:22.30" region="speaker"><metadata ccrow="14" cccol="1"/>SPIKE ON THE SURFACE OF CELLS</p>
  498. <p begin="00:18:22.30" end="00:18:24.93" region="speaker"><metadata ccrow="14" cccol="4"/>AND STAIN FOR BINDING TO</p>
  499. <p begin="00:18:24.93" end="00:18:27.97" region="speaker"><metadata ccrow="14" cccol="0"/>PARTICULAR ANTIBODY MRS SPECIFIC</p>
  500. <p begin="00:18:27.97" end="00:18:28.97" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODIES YOU SEE NO DIFFERENCE</p>
  501. <p begin="00:18:28.97" end="00:18:31.17" region="speaker"><metadata ccrow="14" cccol="4"/>IN BINDING OF ANGIOGENIC</p>
  502. <p begin="00:18:31.17" end="00:18:33.43" region="speaker"><metadata ccrow="14" cccol="1"/>CAPACITY COMPARED TO THE WILD</p>
  503. <p begin="00:18:33.43" end="00:18:35.93" region="speaker"><metadata ccrow="14" cccol="3"/>TYPE SPIKE AND S-2 SPIKE.</p>
  504. <p begin="00:18:35.93" end="00:18:39.13" region="speaker"><metadata ccrow="14" cccol="0"/>THAT S-2P MUTATION DIDN&apos;T RENDER</p>
  505. <p begin="00:18:39.13" end="00:18:40.80" region="speaker"><metadata ccrow="14" cccol="1"/>INEFFECTED BINDING TO DPP 4 SO</p>
  506. <p begin="00:18:40.80" end="00:18:44.50" region="speaker"><metadata ccrow="14" cccol="0"/>WE HAVE A STABILIZED PRE-FUSION</p>
  507. <p begin="00:18:44.50" end="00:18:45.83" region="speaker"><metadata ccrow="14" cccol="1"/>MRS CORONA VIRUS SPIKE PROTEIN</p>
  508. <p begin="00:18:45.83" end="00:18:49.03" region="speaker"><metadata ccrow="14" cccol="1"/>AND NOW WE WANT TO TEST IT FOR</p>
  509. <p begin="00:18:49.03" end="00:18:51.20" region="speaker"><metadata ccrow="14" cccol="2"/>ITS IMMUNOGENICITY IN MICE.</p>
  510. <p begin="00:18:51.20" end="00:18:53.23" region="speaker"><metadata ccrow="14" cccol="0"/>THE FIRST TEST WE DID IS COMPARE</p>
  511. <p begin="00:18:53.23" end="00:18:55.93" region="speaker"><metadata ccrow="14" cccol="1"/>BACK TO S 1 MONOMERIC PROTEIN</p>
  512. <p begin="00:18:55.93" end="00:18:59.10" region="speaker"><metadata ccrow="14" cccol="0"/>AND S WILD TYPE TRIMER AND THE S</p>
  513. <p begin="00:18:59.10" end="00:19:01.47" region="speaker"><metadata ccrow="14" cccol="11"/>2P TRIMER.</p>
  514. <p begin="00:19:01.47" end="00:19:04.27" region="speaker"><metadata ccrow="14" cccol="1"/>WE IMMUNIZE MICE AT WEEK ZERO</p>
  515. <p begin="00:19:04.27" end="00:19:05.70" region="speaker"><metadata ccrow="14" cccol="1"/>AND THREE AND BLEND THOSE MICE</p>
  516. <p begin="00:19:05.70" end="00:19:06.83" region="speaker"><metadata ccrow="14" cccol="0"/>SHORTLY AFTER THE BOOST AND ASK</p>
  517. <p begin="00:19:06.83" end="00:19:08.33" region="speaker"><metadata ccrow="14" cccol="1"/>THE QUESTIONS OF WHAT TYPES OF</p>
  518. <p begin="00:19:08.33" end="00:19:10.80" region="speaker"><metadata ccrow="14" cccol="1"/>ANTIBODIES ARE BEING ELICITED.</p>
  519. <p begin="00:19:10.80" end="00:19:13.00" region="speaker"><metadata ccrow="14" cccol="1"/>SO IN A DOSE PARENT STUDY WHAT</p>
  520. <p begin="00:19:13.00" end="00:19:16.43" region="speaker"><metadata ccrow="14" cccol="2"/>WE SHOWED IS THE S 2P TRIMER</p>
  521. <p begin="00:19:16.43" end="00:19:18.33" region="speaker"><metadata ccrow="14" cccol="4"/>STABILIZED SPIKE ELICITS</p>
  522. <p begin="00:19:18.33" end="00:19:20.37" region="speaker"><metadata ccrow="14" cccol="1"/>ANTIBODIES TO GREATER CAPACITY</p>
  523. <p begin="00:19:20.37" end="00:19:22.70" region="speaker"><metadata ccrow="14" cccol="3"/>TO AUTOLOGOUS CORONA VIRUS</p>
  524. <p begin="00:19:22.70" end="00:19:24.23" region="speaker"><metadata ccrow="14" cccol="0"/>PSEUDOVIRUS STRAINS THEN THE MRS</p>
  525. <p begin="00:19:24.23" end="00:19:26.53" region="speaker"><metadata ccrow="14" cccol="0"/>WILD TYPE AND ALSO THE MRS S 1.</p>
  526. <p begin="00:19:26.53" end="00:19:28.23" region="speaker"><metadata ccrow="14" cccol="1"/>IT WASN&apos;T JUST FOR AUTOLOGOUS</p>
  527. <p begin="00:19:28.23" end="00:19:29.33" region="speaker"><metadata ccrow="14" cccol="3"/>STRAIN BUT ALSO FOR OTHER</p>
  528. <p begin="00:19:29.33" end="00:19:32.57" region="speaker"><metadata ccrow="14" cccol="1"/>STRAINS INCLUDING THE RECENTLY</p>
  529. <p begin="00:19:32.57" end="00:19:35.20" region="speaker"><metadata ccrow="14" cccol="3"/>ISOLATED KOREA 002 STRAIN.</p>
  530. <p begin="00:19:35.20" end="00:19:36.17" region="speaker"><metadata ccrow="14" cccol="1"/>SO WE HAVE THIS SPIKE PROTEIN</p>
  531. <p begin="00:19:36.17" end="00:19:39.33" region="speaker"><metadata ccrow="14" cccol="7"/>THAT ELICITS GREAT</p>
  532. <p begin="00:19:39.33" end="00:19:40.43" region="speaker"><metadata ccrow="14" cccol="2"/>NEUTRALIZATION IN OUR MOUSE</p>
  533. <p begin="00:19:40.43" end="00:19:42.10" region="speaker"><metadata ccrow="14" cccol="1"/>MODEL AND IT&apos;S BETTER THAN ANY</p>
  534. <p begin="00:19:42.10" end="00:19:43.90" region="speaker"><metadata ccrow="14" cccol="1"/>OF THE NEUTRALIZATION WE HAVE</p>
  535. <p begin="00:19:43.90" end="00:19:45.97" region="speaker"><metadata ccrow="14" cccol="1"/>SEEN WITH WILD TYPE SPIKE OR S</p>
  536. <p begin="00:19:45.97" end="00:19:46.13" region="speaker"><metadata ccrow="14" cccol="15"/>1.</p>
  537. <p begin="00:19:46.13" end="00:19:49.53" region="speaker"><metadata ccrow="14" cccol="1"/>IT WASN&apos;T JUST FOR MRS BUT FOR</p>
  538. <p begin="00:19:49.53" end="00:19:52.80" region="speaker"><metadata ccrow="14" cccol="0"/>SARS HKU 1 OC 43 AND A FEW OTHER</p>
  539. <p begin="00:19:52.80" end="00:19:55.70" region="speaker"><metadata ccrow="14" cccol="3"/>SPIKE PROTEINS WE TESTED.</p>
  540. <p begin="00:19:55.70" end="00:19:57.30" region="speaker"><metadata ccrow="14" cccol="0"/>SO WHAT THIS SUGGESTED TO US IS</p>
  541. <p begin="00:19:57.30" end="00:20:00.50" region="speaker"><metadata ccrow="14" cccol="0"/>THAT NOW WITH THOSE TWO PROLINE</p>
  542. <p begin="00:20:00.50" end="00:20:01.80" region="speaker"><metadata ccrow="14" cccol="1"/>MUTATIONS WE HAVE A UNIVERSAL</p>
  543. <p begin="00:20:01.80" end="00:20:04.30" region="speaker"><metadata ccrow="14" cccol="0"/>STRATEGY FOR STABILIZING CORONA</p>
  544. <p begin="00:20:04.30" end="00:20:06.10" region="speaker"><metadata ccrow="14" cccol="1"/>VIRUS SPIKE TRIMERS TO PRODUCE</p>
  545. <p begin="00:20:06.10" end="00:20:09.10" region="speaker"><metadata ccrow="14" cccol="0"/>VACCINE CANDIDATES ESSENTIALLY.</p>
  546. <p begin="00:20:09.10" end="00:20:10.30" region="speaker"><metadata ccrow="14" cccol="3"/>BUT BECAUSE WE ARE AT THE</p>
  547. <p begin="00:20:10.30" end="00:20:11.70" region="speaker"><metadata ccrow="14" cccol="1"/>VACCINE RESEARCH CENTER WE ARE</p>
  548. <p begin="00:20:11.70" end="00:20:13.20" region="speaker"><metadata ccrow="14" cccol="4"/>NEVER SATISFIED WITH THE</p>
  549. <p begin="00:20:13.20" end="00:20:14.20" region="speaker"><metadata ccrow="14" cccol="5"/>ANTIGENS THAT WE HAVE.</p>
  550. <p begin="00:20:14.20" end="00:20:16.20" region="speaker"><metadata ccrow="14" cccol="2"/>AND SO IN COLLABORATION WITH</p>
  551. <p begin="00:20:16.20" end="00:20:18.17" region="speaker"><metadata ccrow="14" cccol="4"/>JASON MCCLELLAN&apos;S LAB AT</p>
  552. <p begin="00:20:18.17" end="00:20:20.70" region="speaker"><metadata ccrow="14" cccol="0"/>DARTMOUTH BUT NOT AT UT AUSTIN,</p>
  553. <p begin="00:20:20.70" end="00:20:23.13" region="speaker"><metadata ccrow="14" cccol="0"/>WE BEGAN TO OPTIMIZE OUR ANTIGEN</p>
  554. <p begin="00:20:23.13" end="00:20:24.67" region="speaker"><metadata ccrow="14" cccol="0"/>DESIGN TO TRY TO HONE IN ON SOME</p>
  555. <p begin="00:20:24.67" end="00:20:26.60" region="speaker"><metadata ccrow="14" cccol="1"/>OF THOSE ANTIBODIESES THAT ARE</p>
  556. <p begin="00:20:26.60" end="00:20:28.33" region="speaker"><metadata ccrow="14" cccol="0"/>OUTSIDE RECEPTOR BINDING DOMAIN.</p>
  557. <p begin="00:20:28.33" end="00:20:30.73" region="speaker"><metadata ccrow="14" cccol="1"/>SO IN DOING THIS, WHAT WE DID</p>
  558. <p begin="00:20:30.73" end="00:20:34.83" region="speaker"><metadata ccrow="14" cccol="0"/>WAS WE REPLACED RECEPTOR BINDING</p>
  559. <p begin="00:20:34.83" end="00:20:37.33" region="speaker"><metadata ccrow="14" cccol="0"/>DOMAIN WITH LINKER REGION AND WE</p>
  560. <p begin="00:20:37.33" end="00:20:39.13" region="speaker"><metadata ccrow="14" cccol="8"/>HAVE DELTA RBD.</p>
  561. <p begin="00:20:39.13" end="00:20:42.03" region="speaker"><metadata ccrow="14" cccol="3"/>IT EXPRESSES WELL IN CELL</p>
  562. <p begin="00:20:42.03" end="00:20:43.13" region="speaker"><metadata ccrow="14" cccol="3"/>CULTURE, HAVE SINGLE PEAK</p>
  563. <p begin="00:20:43.13" end="00:20:46.93" region="speaker"><metadata ccrow="14" cccol="0"/>SIMILAR TO THAT OF THE MRS S 2P.</p>
  564. <p begin="00:20:46.93" end="00:20:49.07" region="speaker"><metadata ccrow="14" cccol="1"/>WE SEE IT ESSENTIALLY FORMS A</p>
  565. <p begin="00:20:49.07" end="00:20:50.97" region="speaker"><metadata ccrow="14" cccol="1"/>PRE-FUSION CONFIRMATION, THERE</p>
  566. <p begin="00:20:50.97" end="00:20:52.67" region="speaker"><metadata ccrow="14" cccol="1"/>IS SPONTANEOUS FLIPPING TO IT</p>
  567. <p begin="00:20:52.67" end="00:20:54.73" region="speaker"><metadata ccrow="14" cccol="0"/>THE POST FUSION CONFIRMATION BY</p>
  568. <p begin="00:20:54.73" end="00:20:57.93" region="speaker"><metadata ccrow="14" cccol="0"/>TAKING OFF HALF THE HEAD REGION.</p>
  569. <p begin="00:20:57.93" end="00:21:00.20" region="speaker"><metadata ccrow="14" cccol="2"/>AND THEN IT BINDS TO ALL THE</p>
  570. <p begin="00:21:00.20" end="00:21:03.07" region="speaker"><metadata ccrow="14" cccol="3"/>ANTIBODIES AND IS EXHIBITS</p>
  571. <p begin="00:21:03.07" end="00:21:07.90" region="speaker"><metadata ccrow="14" cccol="3"/>PROPER ANAGEN IS AT THIS.</p>
  572. <p begin="00:21:07.90" end="00:21:09.00" region="speaker"><metadata ccrow="14" cccol="6"/>ANTIGEN IS AT THIS.</p>
  573. <p begin="00:21:09.00" end="00:21:12.60" region="speaker"><metadata ccrow="14" cccol="1"/>IN A CHALLENGE WITH HUMAN DP 4</p>
  574. <p begin="00:21:12.60" end="00:21:14.90" region="speaker"><metadata ccrow="14" cccol="1"/>RECEPTOR WE TESTED THE MRS IN</p>
  575. <p begin="00:21:14.90" end="00:21:18.83" region="speaker"><metadata ccrow="14" cccol="0"/>COMPARISON TO THE MRS S 2P AND S</p>
  576. <p begin="00:21:18.83" end="00:21:19.60" region="speaker"><metadata ccrow="14" cccol="11"/>1 MONOMER.</p>
  577. <p begin="00:21:19.60" end="00:21:22.30" region="speaker"><metadata ccrow="14" cccol="1"/>ALL THE DATA YOU SEE FROM THE</p>
  578. <p begin="00:21:22.30" end="00:21:23.90" region="speaker"><metadata ccrow="14" cccol="1"/>CHALLENGES TODAY WILL BE DATA</p>
  579. <p begin="00:21:23.90" end="00:21:27.23" region="speaker"><metadata ccrow="14" cccol="0"/>TAKING FROM THE LUNG HARVEST DAY</p>
  580. <p begin="00:21:27.23" end="00:21:30.03" region="speaker"><metadata ccrow="14" cccol="9"/>3 TIME POINT.</p>
  581. <p begin="00:21:30.03" end="00:21:32.27" region="speaker"><metadata ccrow="14" cccol="1"/>SO NOT TO ANYONE&apos;S SURPRISE, I</p>
  582. <p begin="00:21:32.27" end="00:21:34.13" region="speaker"><metadata ccrow="14" cccol="0"/>TOLD YOU IN THAT ONE SLIDE WITH</p>
  583. <p begin="00:21:34.13" end="00:21:35.83" region="speaker"><metadata ccrow="14" cccol="0"/>TABLE OF ALL VACCINES THAT HAVE</p>
  584. <p begin="00:21:35.83" end="00:21:39.33" region="speaker"><metadata ccrow="14" cccol="1"/>BEEN TESTED SO FAR IS EASY TO</p>
  585. <p begin="00:21:39.33" end="00:21:41.03" region="speaker"><metadata ccrow="14" cccol="3"/>ELICIT HUMORAL IMMUNITY AN</p>
  586. <p begin="00:21:41.03" end="00:21:42.73" region="speaker"><metadata ccrow="14" cccol="4"/>VACCINE CANDIDATES HAVE</p>
  587. <p begin="00:21:42.73" end="00:21:43.93" region="speaker"><metadata ccrow="14" cccol="8"/>PROTECTED MICE.</p>
  588. <p begin="00:21:43.93" end="00:21:46.30" region="speaker"><metadata ccrow="14" cccol="0"/>ALL OUR VACCINES THAT WE TESTED</p>
  589. <p begin="00:21:46.30" end="00:21:50.23" region="speaker"><metadata ccrow="14" cccol="0"/>PROTECTED MICE FROM WEIGHT LOSS.</p>
  590. <p begin="00:21:50.23" end="00:21:51.97" region="speaker"><metadata ccrow="14" cccol="1"/>INTERESTINGLY ENOUGH WITH THE</p>
  591. <p begin="00:21:51.97" end="00:21:55.67" region="speaker"><metadata ccrow="14" cccol="0"/>MRS S 2P VACCINE WE SEE DECREASE</p>
  592. <p begin="00:21:55.67" end="00:21:57.23" region="speaker"><metadata ccrow="14" cccol="2"/>IN LUNG VIRAL TITER AT DAY 3</p>
  593. <p begin="00:21:57.23" end="00:22:00.67" region="speaker"><metadata ccrow="14" cccol="1"/>COMPARED TO THAT OF S 1, DELTA</p>
  594. <p begin="00:22:00.67" end="00:22:02.10" region="speaker"><metadata ccrow="14" cccol="1"/>RBD DECREASE IT IS VIRAL TITER</p>
  595. <p begin="00:22:02.10" end="00:22:03.60" region="speaker"><metadata ccrow="14" cccol="12"/>AS WELL.</p>
  596. <p begin="00:22:03.60" end="00:22:05.97" region="speaker"><metadata ccrow="14" cccol="6"/>WHEN WE LOOK AT THE</p>
  597. <p begin="00:22:05.97" end="00:22:07.10" region="speaker"><metadata ccrow="14" cccol="1"/>NEUTRALIZATION CAPACITY AS YOU</p>
  598. <p begin="00:22:07.10" end="00:22:10.80" region="speaker"><metadata ccrow="14" cccol="1"/>WOULD EXPECT EVEN AT LOW DOSE,</p>
  599. <p begin="00:22:10.80" end="00:22:13.60" region="speaker"><metadata ccrow="14" cccol="0"/>THE S 2P IS GREAT NEUTRALIZATION</p>
  600. <p begin="00:22:13.60" end="00:22:14.20" region="speaker"><metadata ccrow="14" cccol="12"/>IN MICE.</p>
  601. <p begin="00:22:14.20" end="00:22:17.33" region="speaker"><metadata ccrow="14" cccol="0"/>ALSO THE MRS S 1 ELICITS MODEST</p>
  602. <p begin="00:22:17.33" end="00:22:19.87" region="speaker"><metadata ccrow="14" cccol="1"/>NEUTRALIZATION IN MICE AS YOU</p>
  603. <p begin="00:22:19.87" end="00:22:20.10" region="speaker"><metadata ccrow="14" cccol="12"/>EXPECT.</p>
  604. <p begin="00:22:20.10" end="00:22:22.33" region="speaker"><metadata ccrow="14" cccol="0"/>WHAT WAS SURPRISING TO US THOUGH</p>
  605. <p begin="00:22:22.33" end="00:22:26.40" region="speaker"><metadata ccrow="14" cccol="0"/>IS THAT EVEN THOUGH THE MRS S 2P</p>
  606. <p begin="00:22:26.40" end="00:22:29.90" region="speaker"><metadata ccrow="14" cccol="1"/>DELTA RBD DOESN&apos;T HAVE A LARGE</p>
  607. <p begin="00:22:29.90" end="00:22:30.80" region="speaker"><metadata ccrow="14" cccol="1"/>NEUTRALIZATION POTENTIAL THESE</p>
  608. <p begin="00:22:30.80" end="00:22:32.47" region="speaker"><metadata ccrow="14" cccol="0"/>MICE WERE STILL PROTECTED THOUGH</p>
  609. <p begin="00:22:32.47" end="00:22:34.53" region="speaker"><metadata ccrow="14" cccol="4"/>MICE THAT DON&apos;T HAVE ANY</p>
  610. <p begin="00:22:34.53" end="00:22:35.77" region="speaker"><metadata ccrow="14" cccol="4"/>NEUTRALIZATION CAPACITY.</p>
  611. <p begin="00:22:35.77" end="00:22:37.67" region="speaker"><metadata ccrow="14" cccol="2"/>SO IT MIGHT NOT NECESSARILY</p>
  612. <p begin="00:22:37.67" end="00:22:39.70" region="speaker"><metadata ccrow="14" cccol="7"/>ALWAYS BE ABOUTN&apos;T</p>
  613. <p begin="00:22:39.70" end="00:22:41.17" region="speaker"><metadata ccrow="14" cccol="0"/>NEUTRALIZATION WITH THESE IS ONE</p>
  614. <p begin="00:22:41.17" end="00:22:42.27" region="speaker"><metadata ccrow="14" cccol="0"/>POINT, THE SECOND POINT IS THAT</p>
  615. <p begin="00:22:42.27" end="00:22:44.17" region="speaker"><metadata ccrow="14" cccol="1"/>THE RECEPTOR BINDING DOMAIN IS</p>
  616. <p begin="00:22:44.17" end="00:22:48.00" region="speaker"><metadata ccrow="14" cccol="0"/>ABSOLUTELY NOT NEEDED TO PROTECT</p>
  617. <p begin="00:22:48.00" end="00:22:49.47" region="speaker"><metadata ccrow="14" cccol="1"/>THESE MICE FROM SUCCUMBING TO</p>
  618. <p begin="00:22:49.47" end="00:22:52.47" region="speaker"><metadata ccrow="14" cccol="5"/>THE CHALLENGE OF MRS.</p>
  619. <p begin="00:22:52.47" end="00:22:55.90" region="speaker"><metadata ccrow="14" cccol="1"/>SO WHAT ANTIBODIES ARE, THERE.</p>
  620. <p begin="00:22:55.90" end="00:22:58.50" region="speaker"><metadata ccrow="14" cccol="0"/>WITH THE HELP OF OLU ALSO IN THE</p>
  621. <p begin="00:22:58.50" end="00:23:02.17" region="speaker"><metadata ccrow="14" cccol="1"/>AUDIENCE, WE DID A LARGE SCALE</p>
  622. <p begin="00:23:02.17" end="00:23:04.77" region="speaker"><metadata ccrow="14" cccol="0"/>DISSECTION -- SORRY, LARGE SCALE</p>
  623. <p begin="00:23:04.77" end="00:23:06.87" region="speaker"><metadata ccrow="14" cccol="2"/>STUDY WHERE WE DISSECTED THE</p>
  624. <p begin="00:23:06.87" end="00:23:08.33" region="speaker"><metadata ccrow="14" cccol="0"/>EPITOPE SPECIFICITY OF THE SERUM</p>
  625. <p begin="00:23:08.33" end="00:23:10.30" region="speaker"><metadata ccrow="14" cccol="3"/>THAT CAME FROM THOSE MICE</p>
  626. <p begin="00:23:10.30" end="00:23:11.13" region="speaker"><metadata ccrow="14" cccol="4"/>IMMUNIZED WITH OUR THREE</p>
  627. <p begin="00:23:11.13" end="00:23:12.13" region="speaker"><metadata ccrow="14" cccol="11"/>VACCINES.</p>
  628. <p begin="00:23:12.13" end="00:23:14.03" region="speaker"><metadata ccrow="14" cccol="2"/>SO I REALLY WANT TO WALK YOU</p>
  629. <p begin="00:23:14.03" end="00:23:15.63" region="speaker"><metadata ccrow="14" cccol="1"/>GUYS THROUGH THIS BECAUSE THE</p>
  630. <p begin="00:23:15.63" end="00:23:18.83" region="speaker"><metadata ccrow="14" cccol="2"/>NEXT FEW SLIDES SHOW ALL THE</p>
  631. <p begin="00:23:18.83" end="00:23:20.23" region="speaker"><metadata ccrow="14" cccol="4"/>DATA IN SOMEWHAT COUNTER</p>
  632. <p begin="00:23:20.23" end="00:23:22.73" region="speaker"><metadata ccrow="14" cccol="0"/>INTUITIVE WAY BY DESCRIBING THE</p>
  633. <p begin="00:23:22.73" end="00:23:25.83" region="speaker"><metadata ccrow="14" cccol="2"/>SERUM AS RBD DEPLETED OR NTD</p>
  634. <p begin="00:23:25.83" end="00:23:27.33" region="speaker"><metadata ccrow="14" cccol="6"/>DEPLETED, SO FORTH.</p>
  635. <p begin="00:23:27.33" end="00:23:31.20" region="speaker"><metadata ccrow="14" cccol="2"/>SO WE BOUND SERUM FROM MICE,</p>
  636. <p begin="00:23:31.20" end="00:23:35.33" region="speaker"><metadata ccrow="14" cccol="0"/>WITH OUR S 2P OR S 1 S 2P DELTA</p>
  637. <p begin="00:23:35.33" end="00:23:38.33" region="speaker"><metadata ccrow="14" cccol="1"/>RBD TO EACH OF THESE PROTEINS,</p>
  638. <p begin="00:23:38.33" end="00:23:40.53" region="speaker"><metadata ccrow="14" cccol="0"/>NON-SPECIFIC RSVF PROTEIN, WHICH</p>
  639. <p begin="00:23:40.53" end="00:23:44.33" region="speaker"><metadata ccrow="14" cccol="1"/>THEN LEAVE ALL THE ANTIBODIES</p>
  640. <p begin="00:23:44.33" end="00:23:47.33" region="speaker"><metadata ccrow="14" cccol="0"/>BEHIND, THE S 2P PROTEIN UNBOUND</p>
  641. <p begin="00:23:47.33" end="00:23:48.53" region="speaker"><metadata ccrow="14" cccol="6"/>ANTIBODIES WOULD BE</p>
  642. <p begin="00:23:48.53" end="00:23:50.00" region="speaker"><metadata ccrow="14" cccol="1"/>NON-EXISTENT, THE S 1 PROTEIN,</p>
  643. <p begin="00:23:50.00" end="00:23:52.60" region="speaker"><metadata ccrow="14" cccol="0"/>THIS IS A MONOMERIC PROTEIN, SO</p>
  644. <p begin="00:23:52.60" end="00:23:55.13" region="speaker"><metadata ccrow="14" cccol="1"/>THE ANTIBODIES WERE QUATERNARY</p>
  645. <p begin="00:23:55.13" end="00:23:56.30" region="speaker"><metadata ccrow="14" cccol="1"/>BINDING BETWEE THE INTERFACES</p>
  646. <p begin="00:23:56.30" end="00:24:01.03" region="speaker"><metadata ccrow="14" cccol="2"/>OF A TRIMER OR S 2 SPECIFIC</p>
  647. <p begin="00:24:01.03" end="00:24:04.80" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODIES, RBD DEPLETION CAUSES</p>
  648. <p begin="00:24:04.80" end="00:24:07.53" region="speaker"><metadata ccrow="14" cccol="3"/>ANTIBODIES TO BE RETAINED</p>
  649. <p begin="00:24:07.53" end="00:24:10.23" region="speaker"><metadata ccrow="14" cccol="1"/>QUANTITYNARY S 2 SPECIFIC AND</p>
  650. <p begin="00:24:10.23" end="00:24:12.23" region="speaker"><metadata ccrow="14" cccol="1"/>ANTI-D DEPLETION LEAVES BEHIND</p>
  651. <p begin="00:24:12.23" end="00:24:14.90" region="speaker"><metadata ccrow="14" cccol="0"/>RBD ANTIBODIES AND S-2 SPECIFIC</p>
  652. <p begin="00:24:14.90" end="00:24:16.00" region="speaker"><metadata ccrow="14" cccol="10"/>ANTIBODIES.</p>
  653. <p begin="00:24:16.00" end="00:24:18.10" region="speaker"><metadata ccrow="14" cccol="0"/>SO WE TOOK THOSE MICE SERUM FROM</p>
  654. <p begin="00:24:18.10" end="00:24:20.80" region="speaker"><metadata ccrow="14" cccol="1"/>MICE THAT WERE IMMUNIZED WITH</p>
  655. <p begin="00:24:20.80" end="00:24:22.90" region="speaker"><metadata ccrow="14" cccol="8"/>THE S 1 VACCINE.</p>
  656. <p begin="00:24:22.90" end="00:24:24.80" region="speaker"><metadata ccrow="14" cccol="1"/>DEPLETED THOSE SERUM AND BOUND</p>
  657. <p begin="00:24:24.80" end="00:24:27.57" region="speaker"><metadata ccrow="14" cccol="0"/>THOSE DEPLETED SERUM TO AN ELISA</p>
  658. <p begin="00:24:27.57" end="00:24:30.80" region="speaker"><metadata ccrow="14" cccol="1"/>PLATE CONTAINING THE MRS S 2P.</p>
  659. <p begin="00:24:30.80" end="00:24:34.00" region="speaker"><metadata ccrow="14" cccol="0"/>WHAT THIS SHOWS IS THAT THE S-1</p>
  660. <p begin="00:24:34.00" end="00:24:35.80" region="speaker"><metadata ccrow="14" cccol="3"/>IMMUNIZED MICE ALL OF THE</p>
  661. <p begin="00:24:35.80" end="00:24:38.40" region="speaker"><metadata ccrow="14" cccol="1"/>ANTIBODIES ARE DEPLETED WITH S</p>
  662. <p begin="00:24:38.40" end="00:24:41.13" region="speaker"><metadata ccrow="14" cccol="3"/>2P AND S-1 AS YOU EXPECT.</p>
  663. <p begin="00:24:41.13" end="00:24:42.13" region="speaker"><metadata ccrow="14" cccol="1"/>INTERESTINGLY ENOUGH WHEN YOU</p>
  664. <p begin="00:24:42.13" end="00:24:44.63" region="speaker"><metadata ccrow="14" cccol="3"/>DEPLETE THOSE SERUM OF NTD</p>
  665. <p begin="00:24:44.63" end="00:24:46.03" region="speaker"><metadata ccrow="14" cccol="0"/>CAPACITY, YOU DON&apos;T DEPLETE OUT</p>
  666. <p begin="00:24:46.03" end="00:24:47.27" region="speaker"><metadata ccrow="14" cccol="2"/>ANY OF THE BINDING CAPACITY</p>
  667. <p begin="00:24:47.27" end="00:24:48.40" region="speaker"><metadata ccrow="14" cccol="13"/>HERE.</p>
  668. <p begin="00:24:48.40" end="00:24:50.93" region="speaker"><metadata ccrow="14" cccol="1"/>BUT WHEN YOU DEPLETE THOSE S 1</p>
  669. <p begin="00:24:50.93" end="00:24:53.33" region="speaker"><metadata ccrow="14" cccol="1"/>IMMUNIZE MOUSE SERUM WITH RBD</p>
  670. <p begin="00:24:53.33" end="00:24:54.33" region="speaker"><metadata ccrow="14" cccol="3"/>BINDING CAPACITY IS GONE.</p>
  671. <p begin="00:24:54.33" end="00:24:56.77" region="speaker"><metadata ccrow="14" cccol="0"/>SO WHAT THAT SAYS IS THAT THE S</p>
  672. <p begin="00:24:56.77" end="00:24:59.03" region="speaker"><metadata ccrow="14" cccol="3"/>1 MONOMERIC VACCINATION IS</p>
  673. <p begin="00:24:59.03" end="00:25:01.10" region="speaker"><metadata ccrow="14" cccol="5"/>ELICITING RBD SPECIFIC</p>
  674. <p begin="00:25:01.10" end="00:25:04.97" region="speaker"><metadata ccrow="14" cccol="7"/>ANTIBODIES MOSTLY.</p>
  675. <p begin="00:25:04.97" end="00:25:06.20" region="speaker"><metadata ccrow="14" cccol="4"/>CONTRAST, OUR STABILIZE</p>
  676. <p begin="00:25:06.20" end="00:25:09.30" region="speaker"><metadata ccrow="14" cccol="0"/>PRE-FUSION MRS TRIMER THE S 2P,</p>
  677. <p begin="00:25:09.30" end="00:25:12.53" region="speaker"><metadata ccrow="14" cccol="0"/>WHEN WE DEPLETE WITH EITHER NTD</p>
  678. <p begin="00:25:12.53" end="00:25:15.50" region="speaker"><metadata ccrow="14" cccol="1"/>OR RBD WE DON&apos;T DEPLETE OUT A</p>
  679. <p begin="00:25:15.50" end="00:25:16.70" region="speaker"><metadata ccrow="14" cccol="1"/>SIGNIFICANT FRACTION OF THOSE</p>
  680. <p begin="00:25:16.70" end="00:25:18.53" region="speaker"><metadata ccrow="14" cccol="6"/>BINDING ANTIBODIES.</p>
  681. <p begin="00:25:18.53" end="00:25:20.47" region="speaker"><metadata ccrow="14" cccol="3"/>NOW WE HAVE A VACCINE THAT</p>
  682. <p begin="00:25:20.47" end="00:25:23.40" region="speaker"><metadata ccrow="14" cccol="1"/>ELICITS ROBUST NEUTRALIZATION</p>
  683. <p begin="00:25:23.40" end="00:25:24.70" region="speaker"><metadata ccrow="14" cccol="1"/>PROTECTS THESE MICE, AND IT&apos;S</p>
  684. <p begin="00:25:24.70" end="00:25:26.80" region="speaker"><metadata ccrow="14" cccol="0"/>DOING IT BY ELICITING ANTIBODIES</p>
  685. <p begin="00:25:26.80" end="00:25:28.30" region="speaker"><metadata ccrow="14" cccol="0"/>OUTSIDE OF THE RECEPTOR BINDING</p>
  686. <p begin="00:25:28.30" end="00:25:28.80" region="speaker"><metadata ccrow="14" cccol="9"/>DOMAIN REGION.</p>
  687. <p begin="00:25:28.80" end="00:25:33.00" region="speaker"><metadata ccrow="14" cccol="2"/>WHICH WAS THE ORIGINAL GOAL.</p>
  688. <p begin="00:25:33.00" end="00:25:34.80" region="speaker"><metadata ccrow="14" cccol="1"/>WHICH OF THOSE ANTIBODIES ARE</p>
  689. <p begin="00:25:34.80" end="00:25:36.87" region="speaker"><metadata ccrow="14" cccol="2"/>RESPONSIBLE FOR PROTECTION?</p>
  690. <p begin="00:25:36.87" end="00:25:39.30" region="speaker"><metadata ccrow="14" cccol="1"/>IN ORDER TO DO THIS INTRICATE</p>
  691. <p begin="00:25:39.30" end="00:25:42.23" region="speaker"><metadata ccrow="14" cccol="0"/>STUDY ONE THING WE HAD TO DO IS</p>
  692. <p begin="00:25:42.23" end="00:25:46.73" region="speaker"><metadata ccrow="14" cccol="3"/>ISOLATE IDG FROM MRS S 2P</p>
  693. <p begin="00:25:46.73" end="00:25:50.63" region="speaker"><metadata ccrow="14" cccol="2"/>IMMUNIZE MICE, TO DO THAT WE</p>
  694. <p begin="00:25:50.63" end="00:25:52.33" region="speaker"><metadata ccrow="14" cccol="2"/>IMMUNIZE MICE WITH VACCINE,</p>
  695. <p begin="00:25:52.33" end="00:25:54.13" region="speaker"><metadata ccrow="14" cccol="4"/>ISOLATED IGG FROM SERUM</p>
  696. <p begin="00:25:54.13" end="00:25:55.80" region="speaker"><metadata ccrow="14" cccol="0"/>COLLECTED OVER A COURSE OF WEEKS</p>
  697. <p begin="00:25:55.80" end="00:25:58.83" region="speaker"><metadata ccrow="14" cccol="1"/>AFTER THE BOOST OF THOSE MICE.</p>
  698. <p begin="00:25:58.83" end="00:26:01.00" region="speaker"><metadata ccrow="14" cccol="0"/>AGAIN REPEATED THOSE DEPLETIONS</p>
  699. <p begin="00:26:01.00" end="00:26:04.67" region="speaker"><metadata ccrow="14" cccol="0"/>BUT THIS TIME ALL THESE UNBOUND</p>
  700. <p begin="00:26:04.67" end="00:26:06.77" region="speaker"><metadata ccrow="14" cccol="1"/>ANTIBODIES WERE THEN PASSIVELY</p>
  701. <p begin="00:26:06.77" end="00:26:09.20" region="speaker"><metadata ccrow="14" cccol="1"/>TRANSFERRED INTO THE CHALLENGE</p>
  702. <p begin="00:26:09.20" end="00:26:11.37" region="speaker"><metadata ccrow="14" cccol="3"/>SYSTEM, AND THE MICE WERE</p>
  703. <p begin="00:26:11.37" end="00:26:13.87" region="speaker"><metadata ccrow="14" cccol="1"/>CHALLENGED 24 HOURS LATER AND</p>
  704. <p begin="00:26:13.87" end="00:26:15.37" region="speaker"><metadata ccrow="14" cccol="0"/>ALL THE TIME POINTS THAT WE TAKE</p>
  705. <p begin="00:26:15.37" end="00:26:17.80" region="speaker"><metadata ccrow="14" cccol="2"/>FOR SURVIVAL WEIGHT LOSS, ET</p>
  706. <p begin="00:26:17.80" end="00:26:19.10" region="speaker"><metadata ccrow="14" cccol="5"/>CETERA, WERE ANALYZED.</p>
  707. <p begin="00:26:19.10" end="00:26:23.03" region="speaker"><metadata ccrow="14" cccol="2"/>IT IS IMPORTANT TO NOTE HERE</p>
  708. <p begin="00:26:23.03" end="00:26:24.87" region="speaker"><metadata ccrow="14" cccol="1"/>BECAUSE TIMES PASSIVE TRANSFER</p>
  709. <p begin="00:26:24.87" end="00:26:26.93" region="speaker"><metadata ccrow="14" cccol="0"/>EXPERIMENTS PEOPLE SEE WHOPPING</p>
  710. <p begin="00:26:26.93" end="00:26:29.13" region="speaker"><metadata ccrow="14" cccol="1"/>DOSES OF IGG GIVEN BACK TO THE</p>
  711. <p begin="00:26:29.13" end="00:26:29.53" region="speaker"><metadata ccrow="14" cccol="13"/>MICE.</p>
  712. <p begin="00:26:29.53" end="00:26:31.30" region="speaker"><metadata ccrow="14" cccol="0"/>HERE WE WERE DILIGENT GIVING THE</p>
  713. <p begin="00:26:31.30" end="00:26:33.67" region="speaker"><metadata ccrow="14" cccol="1"/>MICE ONLY HALF MG OF ANTIBODY</p>
  714. <p begin="00:26:33.67" end="00:26:36.03" region="speaker"><metadata ccrow="14" cccol="1"/>PER MOUSE BECAUSE WE WANTED TO</p>
  715. <p begin="00:26:36.03" end="00:26:37.90" region="speaker"><metadata ccrow="14" cccol="3"/>LOOK AT THE DIFFERENCES IN</p>
  716. <p begin="00:26:37.90" end="00:26:39.03" region="speaker"><metadata ccrow="14" cccol="0"/>PROTECTION BETWEEN THESE GROUPS</p>
  717. <p begin="00:26:39.03" end="00:26:41.93" region="speaker"><metadata ccrow="14" cccol="0"/>AND WE KNEW BASED ON MONOCLONAL</p>
  718. <p begin="00:26:41.93" end="00:26:44.57" region="speaker"><metadata ccrow="14" cccol="1"/>ANTIBODY WORK, THAT PRE-TY LOW</p>
  719. <p begin="00:26:44.57" end="00:26:46.67" region="speaker"><metadata ccrow="14" cccol="0"/>DOSES OF NEUTRALIZING ANTIBODIES</p>
  720. <p begin="00:26:46.67" end="00:26:50.50" region="speaker"><metadata ccrow="14" cccol="6"/>PROTECT THESE MICE.</p>
  721. <p begin="00:26:50.50" end="00:26:52.50" region="speaker"><metadata ccrow="14" cccol="1"/>SO HERE THE DATA OF THE WEIGH</p>
  722. <p begin="00:26:52.50" end="00:26:55.10" region="speaker"><metadata ccrow="14" cccol="0"/>LOSS FROM THE MICE THAT GOT ANY</p>
  723. <p begin="00:26:55.10" end="00:26:57.67" region="speaker"><metadata ccrow="14" cccol="2"/>OF THOSE IGG AND DEPLETED OF</p>
  724. <p begin="00:26:57.67" end="00:26:59.50" region="speaker"><metadata ccrow="14" cccol="3"/>SPECIFIC EPITOPE SUBSETS.</p>
  725. <p begin="00:26:59.50" end="00:27:02.23" region="speaker"><metadata ccrow="14" cccol="0"/>YOU LOOK AT THIS RED LINE, THESE</p>
  726. <p begin="00:27:02.23" end="00:27:05.43" region="speaker"><metadata ccrow="14" cccol="3"/>ARE THE MICE THAT GOT IGG</p>
  727. <p begin="00:27:05.43" end="00:27:08.53" region="speaker"><metadata ccrow="14" cccol="2"/>DEPLETED OF ALL MRS SPECIFIC</p>
  728. <p begin="00:27:08.53" end="00:27:08.90" region="speaker"><metadata ccrow="14" cccol="11"/>ANTIBODY.</p>
  729. <p begin="00:27:08.90" end="00:27:11.73" region="speaker"><metadata ccrow="14" cccol="1"/>AS YOU EXPECT MICE SUCCUMB TO</p>
  730. <p begin="00:27:11.73" end="00:27:12.53" region="speaker"><metadata ccrow="14" cccol="9"/>THE CHALLENGE.</p>
  731. <p begin="00:27:12.53" end="00:27:16.43" region="speaker"><metadata ccrow="14" cccol="1"/>THE MRS S 1 DEPLETED IGGs ALSO</p>
  732. <p begin="00:27:16.43" end="00:27:19.67" region="speaker"><metadata ccrow="14" cccol="1"/>WERE NOT ABLE TO PROTECT THOSE</p>
  733. <p begin="00:27:19.67" end="00:27:20.07" region="speaker"><metadata ccrow="14" cccol="13"/>MICE.</p>
  734. <p begin="00:27:20.07" end="00:27:22.37" region="speaker"><metadata ccrow="14" cccol="3"/>THESE ARE THE HYPOTHETICAL</p>
  735. <p begin="00:27:22.37" end="00:27:23.97" region="speaker"><metadata ccrow="14" cccol="3"/>QUATERNARY OR S 2 SPECIFIC</p>
  736. <p begin="00:27:23.97" end="00:27:25.07" region="speaker"><metadata ccrow="14" cccol="10"/>ANTIBODIES.</p>
  737. <p begin="00:27:25.07" end="00:27:26.73" region="speaker"><metadata ccrow="14" cccol="0"/>INTERESTINGLY ENOUGH IF YOU LOOK</p>
  738. <p begin="00:27:26.73" end="00:27:29.13" region="speaker"><metadata ccrow="14" cccol="1"/>AT THE NTD DEPLETED SUBSET AND</p>
  739. <p begin="00:27:29.13" end="00:27:31.53" region="speaker"><metadata ccrow="14" cccol="0"/>THE RBD DEPLETED SUBSET YOU CAN</p>
  740. <p begin="00:27:31.53" end="00:27:36.67" region="speaker"><metadata ccrow="14" cccol="2"/>SEE THAT THE RD -- B -- RBD</p>
  741. <p begin="00:27:36.67" end="00:27:38.63" region="speaker"><metadata ccrow="14" cccol="3"/>DEPLETED IGG WERE ABLE TO</p>
  742. <p begin="00:27:38.63" end="00:27:41.50" region="speaker"><metadata ccrow="14" cccol="0"/>PROTECT THE MICE AT GREATER THAN</p>
  743. <p begin="00:27:41.50" end="00:27:43.70" region="speaker"><metadata ccrow="14" cccol="2"/>THOSE MICE THAT GOT THE NTD</p>
  744. <p begin="00:27:43.70" end="00:27:45.03" region="speaker"><metadata ccrow="14" cccol="9"/>DEPLETED IGGs.</p>
  745. <p begin="00:27:45.03" end="00:27:47.43" region="speaker"><metadata ccrow="14" cccol="0"/>SO WHAT IS TELLING US IS AT THIS</p>
  746. <p begin="00:27:47.43" end="00:27:50.23" region="speaker"><metadata ccrow="14" cccol="3"/>LOW DOSE THE NTD SPECIFIC</p>
  747. <p begin="00:27:50.23" end="00:27:51.93" region="speaker"><metadata ccrow="14" cccol="1"/>ANTIBODIES ARE MORE PROTECTED</p>
  748. <p begin="00:27:51.93" end="00:27:53.83" region="speaker"><metadata ccrow="14" cccol="1"/>THAN RBD SPECIFIC ANTIBODIES.</p>
  749. <p begin="00:27:53.83" end="00:27:56.93" region="speaker"><metadata ccrow="14" cccol="0"/>WHICH IS SOMETHING THAT WAS VERY</p>
  750. <p begin="00:27:56.93" end="00:27:59.53" region="speaker"><metadata ccrow="14" cccol="0"/>HARD FOR US TO BELIEVE AT FIRST</p>
  751. <p begin="00:27:59.53" end="00:28:02.00" region="speaker"><metadata ccrow="14" cccol="0"/>BECAUSE IT&apos;S INTUITIVE THAT RBD</p>
  752. <p begin="00:28:02.00" end="00:28:03.50" region="speaker"><metadata ccrow="14" cccol="2"/>SPECIFIC ANTIBODIES WOULD BE</p>
  753. <p begin="00:28:03.50" end="00:28:06.30" region="speaker"><metadata ccrow="14" cccol="0"/>EXTREMELY PROTECTED BUT AT THIS</p>
  754. <p begin="00:28:06.30" end="00:28:08.60" region="speaker"><metadata ccrow="14" cccol="0"/>LOW DOSE OF PASSIVE IMMUNIZATION</p>
  755. <p begin="00:28:08.60" end="00:28:10.27" region="speaker"><metadata ccrow="14" cccol="3"/>WE WERE ABLE TO PULL APART</p>
  756. <p begin="00:28:10.27" end="00:28:11.57" region="speaker"><metadata ccrow="14" cccol="2"/>DIFFERENCES IN THE LEVELS OF</p>
  757. <p begin="00:28:11.57" end="00:28:13.77" region="speaker"><metadata ccrow="14" cccol="10"/>PROTECTION.</p>
  758. <p begin="00:28:13.77" end="00:28:15.27" region="speaker"><metadata ccrow="14" cccol="1"/>THE SAME RECAPITULATED WHEN WE</p>
  759. <p begin="00:28:15.27" end="00:28:17.87" region="speaker"><metadata ccrow="14" cccol="0"/>LOOK AT THE VIRAL TITERS HERE IN</p>
  760. <p begin="00:28:17.87" end="00:28:19.47" region="speaker"><metadata ccrow="14" cccol="1"/>THOSE LUNGS THAT WERE TAKEN AT</p>
  761. <p begin="00:28:19.47" end="00:28:24.10" region="speaker"><metadata ccrow="14" cccol="5"/>DAY 3 POST CHALLENGE.</p>
  762. <p begin="00:28:24.10" end="00:28:25.87" region="speaker"><metadata ccrow="14" cccol="1"/>THESE ANTIBODIES WERE THEN --</p>
  763. <p begin="00:28:25.87" end="00:28:28.03" region="speaker"><metadata ccrow="14" cccol="2"/>SORRY A SUBSET OF THESE MICE</p>
  764. <p begin="00:28:28.03" end="00:28:29.40" region="speaker"><metadata ccrow="14" cccol="3"/>WERE BLED RIGHT BEFORE THE</p>
  765. <p begin="00:28:29.40" end="00:28:29.77" region="speaker"><metadata ccrow="14" cccol="11"/>CHALLENGE.</p>
  766. <p begin="00:28:29.77" end="00:28:32.27" region="speaker"><metadata ccrow="14" cccol="0"/>SO THESE ARE NOT NECESSARILY THE</p>
  767. <p begin="00:28:32.27" end="00:28:34.37" region="speaker"><metadata ccrow="14" cccol="0"/>SAME MICE THAT GOT THE CHALLENGE</p>
  768. <p begin="00:28:34.37" end="00:28:35.67" region="speaker"><metadata ccrow="14" cccol="2"/>SO WE CAN&apos;T MAKE CORRELATION</p>
  769. <p begin="00:28:35.67" end="00:28:38.37" region="speaker"><metadata ccrow="14" cccol="0"/>BACK TO PROTECTION IN SUBSETS OF</p>
  770. <p begin="00:28:38.37" end="00:28:41.27" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODIES, WHAT YOU CAN SEE IS</p>
  771. <p begin="00:28:41.27" end="00:28:42.83" region="speaker"><metadata ccrow="14" cccol="4"/>THAT THOSE MICE THAT GOT</p>
  772. <p begin="00:28:42.83" end="00:28:45.03" region="speaker"><metadata ccrow="14" cccol="1"/>PASSIVELY TRANSFERRED WITH IGG</p>
  773. <p begin="00:28:45.03" end="00:28:49.53" region="speaker"><metadata ccrow="14" cccol="0"/>DEPLETED NTD AND RBD DON&apos;T HAVE</p>
  774. <p begin="00:28:49.53" end="00:28:50.63" region="speaker"><metadata ccrow="14" cccol="0"/>SIGNIFICANT DIFFERENCE FOR THEIR</p>
  775. <p begin="00:28:50.63" end="00:28:52.80" region="speaker"><metadata ccrow="14" cccol="0"/>BINDING TITER OF ANTIBODIES WHEN</p>
  776. <p begin="00:28:52.80" end="00:28:55.33" region="speaker"><metadata ccrow="14" cccol="0"/>YOU COMPARE THOSE MICE THAT GOT</p>
  777. <p begin="00:28:55.33" end="00:28:56.47" region="speaker"><metadata ccrow="14" cccol="9"/>MOCK DEPLETED.</p>
  778. <p begin="00:28:56.47" end="00:28:59.00" region="speaker"><metadata ccrow="14" cccol="2"/>SO THERE&apos;S LOADS OF ANTIBODY</p>
  779. <p begin="00:28:59.00" end="00:29:01.60" region="speaker"><metadata ccrow="14" cccol="1"/>THERE BUT BECAUSE OF THAT LOW</p>
  780. <p begin="00:29:01.60" end="00:29:03.63" region="speaker"><metadata ccrow="14" cccol="0"/>DOSE THOSE ANTIBODIES ARE NOT AT</p>
  781. <p begin="00:29:03.63" end="00:29:05.63" region="speaker"><metadata ccrow="14" cccol="1"/>LEAST BY OUR ASSAYS WHICH IS A</p>
  782. <p begin="00:29:05.63" end="00:29:07.50" region="speaker"><metadata ccrow="14" cccol="3"/>SUICIDE ASSAY NOT SHOWING</p>
  783. <p begin="00:29:07.50" end="00:29:08.43" region="speaker"><metadata ccrow="14" cccol="2"/>SIGNIFICANT NEUTRALIZATION.</p>
  784. <p begin="00:29:08.43" end="00:29:10.93" region="speaker"><metadata ccrow="14" cccol="0"/>SO WE ARE PROTECTING THESE MICE</p>
  785. <p begin="00:29:10.93" end="00:29:15.10" region="speaker"><metadata ccrow="14" cccol="1"/>BY ALTERNATIVE, I LIKE TO SAY</p>
  786. <p begin="00:29:15.10" end="00:29:19.80" region="speaker"><metadata ccrow="14" cccol="0"/>RED LINE THAT OUT IN DISCUSSION.</p>
  787. <p begin="00:29:19.80" end="00:29:22.10" region="speaker"><metadata ccrow="14" cccol="1"/>MECHANISM OF PROTECTION, OTHER</p>
  788. <p begin="00:29:22.10" end="00:29:24.07" region="speaker"><metadata ccrow="14" cccol="6"/>THAN NEUTRALIZATION.</p>
  789. <p begin="00:29:24.07" end="00:29:25.93" region="speaker"><metadata ccrow="14" cccol="2"/>SO ONE OF THOSE ANTIBODIES,</p>
  790. <p begin="00:29:25.93" end="00:29:27.13" region="speaker"><metadata ccrow="14" cccol="2"/>THERE&apos;S A COUPLE OF LINES OF</p>
  791. <p begin="00:29:27.13" end="00:29:27.93" region="speaker"><metadata ccrow="14" cccol="2"/>QUESTIONING WE WANTED TO GO</p>
  792. <p begin="00:29:27.93" end="00:29:29.37" region="speaker"><metadata ccrow="14" cccol="13"/>DOWN.</p>
  793. <p begin="00:29:29.37" end="00:29:30.53" region="speaker"><metadata ccrow="14" cccol="5"/>OBVIOUSLY WHAT IS THE</p>
  794. <p begin="00:29:30.53" end="00:29:33.93" region="speaker"><metadata ccrow="14" cccol="2"/>ALTERNATIVE MECHANISM OF --</p>
  795. <p begin="00:29:33.93" end="00:29:35.77" region="speaker"><metadata ccrow="14" cccol="4"/>ALTERNATIVE MECHANISM OF</p>
  796. <p begin="00:29:35.77" end="00:29:36.77" region="speaker"><metadata ccrow="14" cccol="1"/>PROTECTION BUT THEN ALSO WHAT</p>
  797. <p begin="00:29:36.77" end="00:29:39.10" region="speaker"><metadata ccrow="14" cccol="3"/>TYPES OF ANTIBODIES ARE WE</p>
  798. <p begin="00:29:39.10" end="00:29:39.47" region="speaker"><metadata ccrow="14" cccol="11"/>ELICITING.</p>
  799. <p begin="00:29:39.47" end="00:29:40.97" region="speaker"><metadata ccrow="14" cccol="2"/>IF YOU REMEMBER THE PANEL I</p>
  800. <p begin="00:29:40.97" end="00:29:43.70" region="speaker"><metadata ccrow="14" cccol="1"/>SHOWED AT THE BEGINNING OF THE</p>
  801. <p begin="00:29:43.70" end="00:29:45.17" region="speaker"><metadata ccrow="14" cccol="3"/>SLIDE SHOW, LINKS YOU HAD</p>
  802. <p begin="00:29:45.17" end="00:29:48.17" region="speaker"><metadata ccrow="14" cccol="1"/>ALREADY TOLD US VIA HER PAPER</p>
  803. <p begin="00:29:48.17" end="00:29:49.13" region="speaker"><metadata ccrow="14" cccol="4"/>LAST YEAR THAT THERE ARE</p>
  804. <p begin="00:29:49.13" end="00:29:51.43" region="speaker"><metadata ccrow="14" cccol="0"/>ESSENTIALLY THREE CLASSES OF NTD</p>
  805. <p begin="00:29:51.43" end="00:29:54.83" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODIES THAT ARE FOUND IN MRS</p>
  806. <p begin="00:29:54.83" end="00:29:57.47" region="speaker"><metadata ccrow="14" cccol="4"/>SURVIVORS, SO WE TOOK A</p>
  807. <p begin="00:29:57.47" end="00:29:59.23" region="speaker"><metadata ccrow="14" cccol="1"/>POLYCLONAL STRUCTURE ANALOGOUS</p>
  808. <p begin="00:29:59.23" end="00:30:01.57" region="speaker"><metadata ccrow="14" cccol="1"/>-- ANALYSIS APPROACH WITH THE</p>
  809. <p begin="00:30:01.57" end="00:30:03.77" region="speaker"><metadata ccrow="14" cccol="3"/>WAR LAB AT SCRIPPS AND WE</p>
  810. <p begin="00:30:03.77" end="00:30:05.73" region="speaker"><metadata ccrow="14" cccol="2"/>BASICALLY GAVE THEM THE RBD</p>
  811. <p begin="00:30:05.73" end="00:30:07.83" region="speaker"><metadata ccrow="14" cccol="0"/>DEPLETED POLYCLONAL SERUM, THEY</p>
  812. <p begin="00:30:07.83" end="00:30:09.13" region="speaker"><metadata ccrow="14" cccol="2"/>ISOLATED FABS AND THEN BOUND</p>
  813. <p begin="00:30:09.13" end="00:30:13.23" region="speaker"><metadata ccrow="14" cccol="1"/>THOSE FABS TO OUR MRS S 2P AND</p>
  814. <p begin="00:30:13.23" end="00:30:15.23" region="speaker"><metadata ccrow="14" cccol="4"/>ANALYZE STRUCTURE OF THE</p>
  815. <p begin="00:30:15.23" end="00:30:17.63" region="speaker"><metadata ccrow="14" cccol="1"/>POLYCLONAL ANTIBODY RESPONSE.</p>
  816. <p begin="00:30:17.63" end="00:30:19.53" region="speaker"><metadata ccrow="14" cccol="2"/>SO YOU CAN SEE HERE FROM THE</p>
  817. <p begin="00:30:19.53" end="00:30:21.70" region="speaker"><metadata ccrow="14" cccol="0"/>SIDE VIEW OR TOP VIEW, THEY ARE</p>
  818. <p begin="00:30:21.70" end="00:30:23.73" region="speaker"><metadata ccrow="14" cccol="0"/>ESSENTIALLY TWO MAJOR EPITOPES,</p>
  819. <p begin="00:30:23.73" end="00:30:26.47" region="speaker"><metadata ccrow="14" cccol="1"/>THIS YELLOW FAB, AND IN ORANGE</p>
  820. <p begin="00:30:26.47" end="00:30:29.30" region="speaker"><metadata ccrow="14" cccol="1"/>FAB OF NTD ANTIBODIES ELICITED</p>
  821. <p begin="00:30:29.30" end="00:30:32.77" region="speaker"><metadata ccrow="14" cccol="8"/>BY THE MRS S 2P.</p>
  822. <p begin="00:30:32.77" end="00:30:34.50" region="speaker"><metadata ccrow="14" cccol="0"/>THERE&apos;S ALSO ONE CLASS ONLY SEEN</p>
  823. <p begin="00:30:34.50" end="00:30:36.50" region="speaker"><metadata ccrow="14" cccol="0"/>IN ONE CLASS SO WE EXCLUED IT AS</p>
  824. <p begin="00:30:36.50" end="00:30:39.97" region="speaker"><metadata ccrow="14" cccol="3"/>A MAJOR EPITOPE FROM BEING</p>
  825. <p begin="00:30:39.97" end="00:30:42.30" region="speaker"><metadata ccrow="14" cccol="1"/>ENLISTED BY MRS S 2P VACCINE.</p>
  826. <p begin="00:30:42.30" end="00:30:44.90" region="speaker"><metadata ccrow="14" cccol="0"/>WE DID AN OVERLAY OF SOME OF THE</p>
  827. <p begin="00:30:44.90" end="00:30:46.80" region="speaker"><metadata ccrow="14" cccol="1"/>STRUCTURES THAT WE PREVIOUSLY</p>
  828. <p begin="00:30:46.80" end="00:30:48.73" region="speaker"><metadata ccrow="14" cccol="0"/>HAD WITH THE MOORE LAB, WHERE WE</p>
  829. <p begin="00:30:48.73" end="00:30:51.10" region="speaker"><metadata ccrow="14" cccol="0"/>GAVE THEM MONOCLONAL ANTIBODIES</p>
  830. <p begin="00:30:51.10" end="00:30:54.67" region="speaker"><metadata ccrow="14" cccol="1"/>TO LOOK AT BINDING OF REVENUES</p>
  831. <p begin="00:30:54.67" end="00:30:55.93" region="speaker"><metadata ccrow="14" cccol="1"/>OF THOSE MOB CLONAL ANTIBODIES</p>
  832. <p begin="00:30:55.93" end="00:30:58.27" region="speaker"><metadata ccrow="14" cccol="0"/>ON OUR -- MONOCLONAL ANTIBODIES</p>
  833. <p begin="00:30:58.27" end="00:31:00.33" region="speaker"><metadata ccrow="14" cccol="6"/>ON THE MRS ANTIGEN.</p>
  834. <p begin="00:31:00.33" end="00:31:01.33" region="speaker"><metadata ccrow="14" cccol="2"/>THIS CLASS ONE WHICH IS SEEN</p>
  835. <p begin="00:31:01.33" end="00:31:04.47" region="speaker"><metadata ccrow="14" cccol="0"/>HERE IN YELLOW, SEEMS TO OVERLAP</p>
  836. <p begin="00:31:04.47" end="00:31:06.57" region="speaker"><metadata ccrow="14" cccol="2"/>WITH THE SIMILAR EPITOPE AT</p>
  837. <p begin="00:31:06.57" end="00:31:08.43" region="speaker"><metadata ccrow="14" cccol="3"/>EITHER THE G2 WHICH IS THE</p>
  838. <p begin="00:31:08.43" end="00:31:11.37" region="speaker"><metadata ccrow="14" cccol="1"/>PURPLE OR THE GC 57 MONOCLONAL</p>
  839. <p begin="00:31:11.37" end="00:31:12.77" region="speaker"><metadata ccrow="14" cccol="5"/>ANTIBODY SEEN IN PINK.</p>
  840. <p begin="00:31:12.77" end="00:31:13.97" region="speaker"><metadata ccrow="14" cccol="2"/>THE GREEN CLASS ALTHOUGH WE</p>
  841. <p begin="00:31:13.97" end="00:31:16.07" region="speaker"><metadata ccrow="14" cccol="0"/>DON&apos;T NECESSARILY KNOW THIS, IS</p>
  842. <p begin="00:31:16.07" end="00:31:18.33" region="speaker"><metadata ccrow="14" cccol="1"/>PROBABLY WE&apos;RE THINKING EITHER</p>
  843. <p begin="00:31:18.33" end="00:31:23.27" region="speaker"><metadata ccrow="14" cccol="1"/>AN A-2 LIGHT OR A-10 LIKE NTD</p>
  844. <p begin="00:31:23.27" end="00:31:27.53" region="speaker"><metadata ccrow="14" cccol="7"/>SPECIFIC ANTIBODY.</p>
  845. <p begin="00:31:27.53" end="00:31:31.80" region="speaker"><metadata ccrow="14" cccol="1"/>SO WE KNOW THESE TYPES OF G-2s</p>
  846. <p begin="00:31:31.80" end="00:31:36.30" region="speaker"><metadata ccrow="14" cccol="0"/>AND JC 5713 ANTIBODIES HAVE HIGH</p>
  847. <p begin="00:31:36.30" end="00:31:38.23" region="speaker"><metadata ccrow="14" cccol="4"/>LEVELS OF NEUTRALIZATION</p>
  848. <p begin="00:31:38.23" end="00:31:38.60" region="speaker"><metadata ccrow="14" cccol="11"/>POTENTIAL.</p>
  849. <p begin="00:31:38.60" end="00:31:40.00" region="speaker"><metadata ccrow="14" cccol="1"/>SO ANOTHER TRAIN OF THOUGHT AS</p>
  850. <p begin="00:31:40.00" end="00:31:41.00" region="speaker"><metadata ccrow="14" cccol="4"/>WE HAVE BEEN LOOKING AT</p>
  851. <p begin="00:31:41.00" end="00:31:42.03" region="speaker"><metadata ccrow="14" cccol="2"/>MECHANISMS OF PROTECTION FOR</p>
  852. <p begin="00:31:42.03" end="00:31:44.40" region="speaker"><metadata ccrow="14" cccol="1"/>THESE ANTIBODIES, WE HAVE BEEN</p>
  853. <p begin="00:31:44.40" end="00:31:47.90" region="speaker"><metadata ccrow="14" cccol="6"/>LOOKING AT IT FROM A</p>
  854. <p begin="00:31:47.90" end="00:31:49.17" region="speaker"><metadata ccrow="14" cccol="1"/>NEUTRALIZATION STANDPOINT, HOW</p>
  855. <p begin="00:31:49.17" end="00:31:51.13" region="speaker"><metadata ccrow="14" cccol="1"/>ARE THE ANTIBODIES THAT DON&apos;T</p>
  856. <p begin="00:31:51.13" end="00:31:53.43" region="speaker"><metadata ccrow="14" cccol="0"/>BIND IN RECEPTOR BINDING DOMAIN</p>
  857. <p begin="00:31:53.43" end="00:31:54.93" region="speaker"><metadata ccrow="14" cccol="2"/>NEUTRALIZING TO THE SAME OR</p>
  858. <p begin="00:31:54.93" end="00:31:56.63" region="speaker"><metadata ccrow="14" cccol="2"/>GREATER POTENTIAL THAN THOSE</p>
  859. <p begin="00:31:56.63" end="00:31:57.90" region="speaker"><metadata ccrow="14" cccol="3"/>ANTIBODIES THAT DO BIND IN</p>
  860. <p begin="00:31:57.90" end="00:32:00.73" region="speaker"><metadata ccrow="14" cccol="4"/>RECEPTOR BINDING DOMAIN.</p>
  861. <p begin="00:32:00.73" end="00:32:03.00" region="speaker"><metadata ccrow="14" cccol="2"/>HERE WITH HELP OF A VISITING</p>
  862. <p begin="00:32:03.00" end="00:32:04.47" region="speaker"><metadata ccrow="14" cccol="4"/>SCIENCE IN THE LAB, WHO</p>
  863. <p begin="00:32:04.47" end="00:32:06.27" region="speaker"><metadata ccrow="14" cccol="0"/>DEVELOPED A CELL SURFACE BINDING</p>
  864. <p begin="00:32:06.27" end="00:32:08.67" region="speaker"><metadata ccrow="14" cccol="2"/>ASSAY WHICH IS AN CYTOMETRY</p>
  865. <p begin="00:32:08.67" end="00:32:11.60" region="speaker"><metadata ccrow="14" cccol="2"/>ASSAY WHERE WE EXPRESS DPP 4</p>
  866. <p begin="00:32:11.60" end="00:32:14.70" region="speaker"><metadata ccrow="14" cccol="2"/>SURFACE OF CELLS AND ABLE TO</p>
  867. <p begin="00:32:14.70" end="00:32:16.00" region="speaker"><metadata ccrow="14" cccol="0"/>COMBINE ANTIBODIES WITH A SPIKE</p>
  868. <p begin="00:32:16.00" end="00:32:17.00" region="speaker"><metadata ccrow="14" cccol="3"/>PROTEIN AND ASK ABOUT THE</p>
  869. <p begin="00:32:17.00" end="00:32:22.70" region="speaker"><metadata ccrow="14" cccol="0"/>PERCENT OF INHIBITION, TO DE-54.</p>
  870. <p begin="00:32:22.70" end="00:32:25.57" region="speaker"><metadata ccrow="14" cccol="0"/>YOU CAN SEE G-2 IDD AND FABS ARE</p>
  871. <p begin="00:32:25.57" end="00:32:28.37" region="speaker"><metadata ccrow="14" cccol="1"/>ABLE TO INHIBIT MRS BY BINDING</p>
  872. <p begin="00:32:28.37" end="00:32:31.43" region="speaker"><metadata ccrow="14" cccol="0"/>TO THE FUNCTIONAL DE5 H RECEPTOR</p>
  873. <p begin="00:32:31.43" end="00:32:33.10" region="speaker"><metadata ccrow="14" cccol="6"/>ON SURFACE OF CELLS.</p>
  874. <p begin="00:32:33.10" end="00:32:34.87" region="speaker"><metadata ccrow="14" cccol="2"/>A PAPER THAT IS CURRENTLY IN</p>
  875. <p begin="00:32:34.87" end="00:32:36.97" region="speaker"><metadata ccrow="14" cccol="2"/>REVIEW RIGHT NOW, THE WAY WE</p>
  876. <p begin="00:32:36.97" end="00:32:38.97" region="speaker"><metadata ccrow="14" cccol="5"/>SUGGESTED THIS TYPE OF</p>
  877. <p begin="00:32:38.97" end="00:32:41.07" region="speaker"><metadata ccrow="14" cccol="1"/>NEUTRALIZATION IS HAPPENING IS</p>
  878. <p begin="00:32:41.07" end="00:32:43.27" region="speaker"><metadata ccrow="14" cccol="0"/>THAT ESSENTIALLY AS YOU CAN SEE</p>
  879. <p begin="00:32:43.27" end="00:32:44.97" region="speaker"><metadata ccrow="14" cccol="1"/>HERE ALTHOUGH THE FAB DOESN&apos;T</p>
  880. <p begin="00:32:44.97" end="00:32:48.10" region="speaker"><metadata ccrow="14" cccol="0"/>HAVE THE ABILITY TO CLASH WITH D</p>
  881. <p begin="00:32:48.10" end="00:32:50.47" region="speaker"><metadata ccrow="14" cccol="1"/>54 BINDING WE THINK THERE&apos;S A</p>
  882. <p begin="00:32:50.47" end="00:32:54.97" region="speaker"><metadata ccrow="14" cccol="1"/>CLASH OF THE G-2 IDGs WITH THE</p>
  883. <p begin="00:32:54.97" end="00:32:58.10" region="speaker"><metadata ccrow="14" cccol="0"/>D 5 # CELLULAR RECEPTOR IN A WAY</p>
  884. <p begin="00:32:58.10" end="00:32:59.90" region="speaker"><metadata ccrow="14" cccol="1"/>THAT WE HAVE TO ELUCIDATE THE</p>
  885. <p begin="00:32:59.90" end="00:33:04.77" region="speaker"><metadata ccrow="14" cccol="1"/>REAL KINETICS OR MECHANISMS OF</p>
  886. <p begin="00:33:04.77" end="00:33:05.87" region="speaker"><metadata ccrow="14" cccol="10"/>THAT CLASH.</p>
  887. <p begin="00:33:05.87" end="00:33:07.10" region="speaker"><metadata ccrow="14" cccol="0"/>THERE ALSO MIGHT BE THE ABILITY</p>
  888. <p begin="00:33:07.10" end="00:33:11.03" region="speaker"><metadata ccrow="14" cccol="1"/>TO G2 IGG TO CROSS LINK SPIKE</p>
  889. <p begin="00:33:11.03" end="00:33:12.83" region="speaker"><metadata ccrow="14" cccol="4"/>PROTEINS AND THEN CAUSE</p>
  890. <p begin="00:33:12.83" end="00:33:15.37" region="speaker"><metadata ccrow="14" cccol="4"/>NEUTRALIZATION THAT WAY.</p>
  891. <p begin="00:33:15.37" end="00:33:17.37" region="speaker"><metadata ccrow="14" cccol="1"/>SO IN THE SECOND PART OF THIS</p>
  892. <p begin="00:33:17.37" end="00:33:19.80" region="speaker"><metadata ccrow="14" cccol="0"/>TALK, WE CAN CONCLUDE THAT MRS S</p>
  893. <p begin="00:33:19.80" end="00:33:22.37" region="speaker"><metadata ccrow="14" cccol="2"/>2 TRIMERS ELICIT ANTIBODIES</p>
  894. <p begin="00:33:22.37" end="00:33:26.53" region="speaker"><metadata ccrow="14" cccol="0"/>SPECIFIC FOR NTD AND RBD REASONS</p>
  895. <p begin="00:33:26.53" end="00:33:30.23" region="speaker"><metadata ccrow="14" cccol="2"/>I LIKE TO KEEP IT OUT BUT WE</p>
  896. <p begin="00:33:30.23" end="00:33:31.93" region="speaker"><metadata ccrow="14" cccol="2"/>HAVE SHOWN SOME CALCULATIONS</p>
  897. <p begin="00:33:31.93" end="00:33:34.83" region="speaker"><metadata ccrow="14" cccol="1"/>THAT WE DO SEE UPWARDS OF S-2</p>
  898. <p begin="00:33:34.83" end="00:33:38.37" region="speaker"><metadata ccrow="14" cccol="0"/>SPECIFIC ANTIBODIES ELICITED BY</p>
  899. <p begin="00:33:38.37" end="00:33:42.70" region="speaker"><metadata ccrow="14" cccol="4"/>MRS TRIMER AS WELL T. IT</p>
  900. <p begin="00:33:42.70" end="00:33:44.27" region="speaker"><metadata ccrow="14" cccol="4"/>HELISITS TWO CLASSES OF</p>
  901. <p begin="00:33:44.27" end="00:33:47.70" region="speaker"><metadata ccrow="14" cccol="5"/>ANTIBODIES, ONE IS THE</p>
  902. <p begin="00:33:47.70" end="00:33:49.40" region="speaker"><metadata ccrow="14" cccol="3"/>NEUTRALIZING G 5713 CLASS</p>
  903. <p begin="00:33:49.40" end="00:33:51.43" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODIES. THOSE ANTI-BOUGH DO</p>
  904. <p begin="00:33:51.43" end="00:33:52.93" region="speaker"><metadata ccrow="14" cccol="1"/>DIS HAVE BEEN SHOWN IN OUR LAB</p>
  905. <p begin="00:33:52.93" end="00:33:55.83" region="speaker"><metadata ccrow="14" cccol="1"/>AND ALSO IN MOAN CLONAL LAB TO</p>
  906. <p begin="00:33:55.83" end="00:33:57.93" region="speaker"><metadata ccrow="14" cccol="1"/>NEUTRALIZE MRS CORONA VIRUS BY</p>
  907. <p begin="00:33:57.93" end="00:34:00.90" region="speaker"><metadata ccrow="14" cccol="2"/>BLOCKING ACCESS TO D 54 IN A</p>
  908. <p begin="00:34:00.90" end="00:34:01.70" region="speaker"><metadata ccrow="14" cccol="3"/>MECHANISM STILL TRYING TO</p>
  909. <p begin="00:34:01.70" end="00:34:04.10" region="speaker"><metadata ccrow="14" cccol="11"/>DECIPHER.</p>
  910. <p begin="00:34:04.10" end="00:34:06.10" region="speaker"><metadata ccrow="14" cccol="0"/>NTD SPECIFIC ANTIBODIES ARE MORE</p>
  911. <p begin="00:34:06.10" end="00:34:08.70" region="speaker"><metadata ccrow="14" cccol="2"/>PROTECTIVE THAN RBD SPECIFIC</p>
  912. <p begin="00:34:08.70" end="00:34:11.90" region="speaker"><metadata ccrow="14" cccol="1"/>ANTIBODIES IN CHALLENGE SYSTEM</p>
  913. <p begin="00:34:11.90" end="00:34:18.60" region="speaker"><metadata ccrow="14" cccol="0"/>EVEN AT SUBNEUTRALLIZING LEVEL.</p>
  914. <p begin="00:34:18.60" end="00:34:21.87" region="speaker"><metadata ccrow="14" cccol="0"/>OF THE ANTIBODIES AND OF COURSE</p>
  915. <p begin="00:34:21.87" end="00:34:23.73" region="speaker"><metadata ccrow="14" cccol="0"/>THE VACCINE RESEARCH CENTER, WE</p>
  916. <p begin="00:34:23.73" end="00:34:25.47" region="speaker"><metadata ccrow="14" cccol="3"/>ARE OPTIMIZING OUR ANTIGEN</p>
  917. <p begin="00:34:25.47" end="00:34:28.07" region="speaker"><metadata ccrow="14" cccol="0"/>DESIGN AND IMPROVING THE VACCINE</p>
  918. <p begin="00:34:28.07" end="00:34:29.57" region="speaker"><metadata ccrow="14" cccol="4"/>PLATFORMS FOR HONING OUR</p>
  919. <p begin="00:34:29.57" end="00:34:35.27" region="speaker"><metadata ccrow="14" cccol="0"/>INTEREST ON TO THOSE EPITOPES OF</p>
  920. <p begin="00:34:35.27" end="00:34:37.10" region="speaker"><metadata ccrow="14" cccol="7"/>SPECIFIC INTEREST.</p>
  921. <p begin="00:34:37.10" end="00:34:40.20" region="speaker"><metadata ccrow="14" cccol="0"/>AS WE THINK ABOUT HOW THESE NTD</p>
  922. <p begin="00:34:40.20" end="00:34:43.40" region="speaker"><metadata ccrow="14" cccol="2"/>ANTIBODIES MIGHT BE WORKING,</p>
  923. <p begin="00:34:43.40" end="00:34:45.57" region="speaker"><metadata ccrow="14" cccol="5"/>OTHER THAN BY TYPICAL</p>
  924. <p begin="00:34:45.57" end="00:34:47.60" region="speaker"><metadata ccrow="14" cccol="0"/>NEUTRALIZATION MECHANISMS WE ARE</p>
  925. <p begin="00:34:47.60" end="00:34:50.03" region="speaker"><metadata ccrow="14" cccol="0"/>STARTING TO EXPLORE FT MEDIATED</p>
  926. <p begin="00:34:50.03" end="00:34:51.93" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODY FUNCTIONS WHICH IS FOR</p>
  927. <p begin="00:34:51.93" end="00:34:55.57" region="speaker"><metadata ccrow="14" cccol="0"/>ME THE LEADING PROBABLY IDEA OR</p>
  928. <p begin="00:34:55.57" end="00:34:57.07" region="speaker"><metadata ccrow="14" cccol="2"/>HYPOTHESIS HERE&apos;S SPECIALLY</p>
  929. <p begin="00:34:57.07" end="00:34:59.97" region="speaker"><metadata ccrow="14" cccol="0"/>BECAUSE OF THE DATA WE SEE WHERE</p>
  930. <p begin="00:34:59.97" end="00:35:02.03" region="speaker"><metadata ccrow="14" cccol="2"/>THERE IS PREVENTION OF VIRAL</p>
  931. <p begin="00:35:02.03" end="00:35:04.67" region="speaker"><metadata ccrow="14" cccol="2"/>ESCAPE IN VITRO AND IN VIVO.</p>
  932. <p begin="00:35:04.67" end="00:35:08.27" region="speaker"><metadata ccrow="14" cccol="3"/>THE EXTENT OF WHICH WE CAN</p>
  933. <p begin="00:35:08.27" end="00:35:12.43" region="speaker"><metadata ccrow="14" cccol="0"/>INHIBIT SIALIC ACID WITH BINDING</p>
  934. <p begin="00:35:12.43" end="00:35:13.93" region="speaker"><metadata ccrow="14" cccol="3"/>ANTIBODIES AND THOUGH NOT</p>
  935. <p begin="00:35:13.93" end="00:35:15.43" region="speaker"><metadata ccrow="14" cccol="2"/>NECESSARILY CO-RECEPTOR THAT</p>
  936. <p begin="00:35:15.43" end="00:35:17.97" region="speaker"><metadata ccrow="14" cccol="1"/>COULD BE PROVEN OVER AND OVER</p>
  937. <p begin="00:35:17.97" end="00:35:21.07" region="speaker"><metadata ccrow="14" cccol="2"/>AGAIN, FOR MRS OR ATTACHMENT</p>
  938. <p begin="00:35:21.07" end="00:35:22.40" region="speaker"><metadata ccrow="14" cccol="1"/>FACTORS WE STILL HAVE TO THINK</p>
  939. <p begin="00:35:22.40" end="00:35:26.70" region="speaker"><metadata ccrow="14" cccol="1"/>ABOUT NTD SPECIFIC ANTIBODIES</p>
  940. <p begin="00:35:26.70" end="00:35:28.70" region="speaker"><metadata ccrow="14" cccol="4"/>BLOCKING CO-RECEPTOR AS</p>
  941. <p begin="00:35:28.70" end="00:35:29.90" region="speaker"><metadata ccrow="14" cccol="4"/>MECHANISM FOR PROTECTION</p>
  942. <p begin="00:35:29.90" end="00:35:34.13" region="speaker"><metadata ccrow="14" cccol="6"/>ESPECIALLY IN VIVO.</p>
  943. <p begin="00:35:34.13" end="00:35:35.97" region="speaker"><metadata ccrow="14" cccol="2"/>THEN MOVING FORWARD WITH OUR</p>
  944. <p begin="00:35:35.97" end="00:35:37.60" region="speaker"><metadata ccrow="14" cccol="1"/>ANTIGEN THAT SEEMS TO BE VERY</p>
  945. <p begin="00:35:37.60" end="00:35:40.00" region="speaker"><metadata ccrow="14" cccol="6"/>ROBUST EITHER FROM A</p>
  946. <p begin="00:35:40.00" end="00:35:41.67" region="speaker"><metadata ccrow="14" cccol="3"/>NEUTRALIZATION STANDPOINT,</p>
  947. <p begin="00:35:41.67" end="00:35:42.60" region="speaker"><metadata ccrow="14" cccol="0"/>PARTICULARLY THINKING ABOUT THE</p>
  948. <p begin="00:35:42.60" end="00:35:46.00" region="speaker"><metadata ccrow="14" cccol="0"/>FACT THAT WE CAN ELICIT OUTSIDE</p>
  949. <p begin="00:35:46.00" end="00:35:47.30" region="speaker"><metadata ccrow="14" cccol="0"/>THE RECEPTOR BINDING DOMAIN, WE</p>
  950. <p begin="00:35:47.30" end="00:35:49.80" region="speaker"><metadata ccrow="14" cccol="0"/>HAVE TAKEN OUR ANTIGEN DESIGN A</p>
  951. <p begin="00:35:49.80" end="00:35:52.33" region="speaker"><metadata ccrow="14" cccol="0"/>TAD FURTHER TO TRY TO HONE IN ON</p>
  952. <p begin="00:35:52.33" end="00:35:55.23" region="speaker"><metadata ccrow="14" cccol="3"/>THOSE MORE CROSS REACTIVE</p>
  953. <p begin="00:35:55.23" end="00:35:56.97" region="speaker"><metadata ccrow="14" cccol="1"/>EPITOPES WE ARE DISPLAYING OUR</p>
  954. <p begin="00:35:56.97" end="00:35:59.57" region="speaker"><metadata ccrow="14" cccol="5"/>ANTIGEN ON SURFACE OF</p>
  955. <p begin="00:35:59.57" end="00:36:02.87" region="speaker"><metadata ccrow="14" cccol="1"/>NANOPARTICLES AND ALSO WE IN A</p>
  956. <p begin="00:36:02.87" end="00:36:04.57" region="speaker"><metadata ccrow="14" cccol="0"/>COLLABORATION WITH -- DELIVERING</p>
  957. <p begin="00:36:04.57" end="00:36:08.27" region="speaker"><metadata ccrow="14" cccol="8"/>THESE VIA mRNA.</p>
  958. <p begin="00:36:08.27" end="00:36:09.97" region="speaker"><metadata ccrow="14" cccol="0"/>SO I BRIEFLY WANT TO TALK ABOUT</p>
  959. <p begin="00:36:09.97" end="00:36:14.00" region="speaker"><metadata ccrow="14" cccol="1"/>PROOF OF CONCEPT HERE, BECAUSE</p>
  960. <p begin="00:36:14.00" end="00:36:16.30" region="speaker"><metadata ccrow="14" cccol="1"/>IT IS PART OF THE WORK THAT I</p>
  961. <p begin="00:36:16.30" end="00:36:17.77" region="speaker"><metadata ccrow="14" cccol="0"/>HAVE BEEN DOING AND THE VACCINE</p>
  962. <p begin="00:36:17.77" end="00:36:21.17" region="speaker"><metadata ccrow="14" cccol="1"/>RESEARCH CENTER IS LOOKING AT</p>
  963. <p begin="00:36:21.17" end="00:36:23.47" region="speaker"><metadata ccrow="14" cccol="2"/>REMOVING THE IMMUNODOMINANT</p>
  964. <p begin="00:36:23.47" end="00:36:25.17" region="speaker"><metadata ccrow="14" cccol="1"/>INFLUENZA HA HEAD TO EXPOSE A</p>
  965. <p begin="00:36:25.17" end="00:36:26.53" region="speaker"><metadata ccrow="14" cccol="1"/>STEM, A CONCEPT WE ALSO WANTED</p>
  966. <p begin="00:36:26.53" end="00:36:28.33" region="speaker"><metadata ccrow="14" cccol="2"/>TO MOVE FORWARD WITH CORONA</p>
  967. <p begin="00:36:28.33" end="00:36:30.43" region="speaker"><metadata ccrow="14" cccol="9"/>VIRUS AS WELL.</p>
  968. <p begin="00:36:30.43" end="00:36:33.53" region="speaker"><metadata ccrow="14" cccol="0"/>PARTICULARLY SEEING THAT THE MRS</p>
  969. <p begin="00:36:33.53" end="00:36:37.63" region="speaker"><metadata ccrow="14" cccol="2"/>S 2P TRIMER DOES NOT ELICIT</p>
  970. <p begin="00:36:37.63" end="00:36:39.53" region="speaker"><metadata ccrow="14" cccol="2"/>GREAT S 2, SPECIFIC ANTIBODY</p>
  971. <p begin="00:36:39.53" end="00:36:41.13" region="speaker"><metadata ccrow="14" cccol="11"/>RESPONSES.</p>
  972. <p begin="00:36:41.13" end="00:36:44.83" region="speaker"><metadata ccrow="14" cccol="1"/>IN COLLABORATION WITH JEFFREY</p>
  973. <p begin="00:36:44.83" end="00:36:47.03" region="speaker"><metadata ccrow="14" cccol="2"/>BOYINGTON, AND ET CETERA, WE</p>
  974. <p begin="00:36:47.03" end="00:36:50.73" region="speaker"><metadata ccrow="14" cccol="1"/>WERE ABLE TO DESIGN A VACCINE</p>
  975. <p begin="00:36:50.73" end="00:36:53.83" region="speaker"><metadata ccrow="14" cccol="1"/>CONSTRUCT THAT IS A STABILIZED</p>
  976. <p begin="00:36:53.83" end="00:36:54.93" region="speaker"><metadata ccrow="14" cccol="5"/>INFLUENZA HA STEM AND</p>
  977. <p begin="00:36:54.93" end="00:37:00.90" region="speaker"><metadata ccrow="14" cccol="1"/>ESSENTIALLY WHAT WE DID IS WE</p>
  978. <p begin="00:37:00.90" end="00:37:03.57" region="speaker"><metadata ccrow="14" cccol="4"/>REPLACE THE HA HEAD WITH</p>
  979. <p begin="00:37:03.57" end="00:37:06.47" region="speaker"><metadata ccrow="14" cccol="4"/>DISULFIDE BINDED LOP AND</p>
  980. <p begin="00:37:06.47" end="00:37:08.27" region="speaker"><metadata ccrow="14" cccol="4"/>REPACKENING RESURFACING</p>
  981. <p begin="00:37:08.27" end="00:37:09.07" region="speaker"><metadata ccrow="14" cccol="3"/>MUTATIONS, ET CETERA, AND</p>
  982. <p begin="00:37:09.07" end="00:37:10.10" region="speaker"><metadata ccrow="14" cccol="1"/>EXPRESS THE STABILIZED VERSION</p>
  983. <p begin="00:37:10.10" end="00:37:12.83" region="speaker"><metadata ccrow="14" cccol="1"/>OF THIS HA STEM ON THE SURFACE</p>
  984. <p begin="00:37:12.83" end="00:37:14.67" region="speaker"><metadata ccrow="14" cccol="1"/>OF A NANOPARTICLE AND EXPLORED</p>
  985. <p begin="00:37:14.67" end="00:37:15.80" region="speaker"><metadata ccrow="14" cccol="6"/>THE IMMUNOGENICITY.</p>
  986. <p begin="00:37:15.80" end="00:37:19.20" region="speaker"><metadata ccrow="14" cccol="0"/>TAKING SOME OF THOSE STRATEGIES,</p>
  987. <p begin="00:37:19.20" end="00:37:20.90" region="speaker"><metadata ccrow="14" cccol="3"/>BACK INTO THE CORONA VIRUS</p>
  988. <p begin="00:37:20.90" end="00:37:22.60" region="speaker"><metadata ccrow="14" cccol="3"/>SYSTEM WE ACTUALLY NOW AS</p>
  989. <p begin="00:37:22.60" end="00:37:25.00" region="speaker"><metadata ccrow="14" cccol="1"/>RECENTLY BEEN ABLE TO SUCCESS</p>
  990. <p begin="00:37:25.00" end="00:37:26.60" region="speaker"><metadata ccrow="14" cccol="1"/>FRIDAY EXPRESS THE STABILIZED</p>
  991. <p begin="00:37:26.60" end="00:37:29.50" region="speaker"><metadata ccrow="14" cccol="4"/>VERSION OF THE MRS S 1.</p>
  992. <p begin="00:37:29.50" end="00:37:31.30" region="speaker"><metadata ccrow="14" cccol="0"/>AND IT IS IN MICE RIGHT NOW AND</p>
  993. <p begin="00:37:31.30" end="00:37:33.50" region="speaker"><metadata ccrow="14" cccol="6"/>WE WILL LOOK AT THE</p>
  994. <p begin="00:37:33.50" end="00:37:34.57" region="speaker"><metadata ccrow="14" cccol="1"/>IMMUNOGENICITY OF THAT AND SEE</p>
  995. <p begin="00:37:34.57" end="00:37:37.07" region="speaker"><metadata ccrow="14" cccol="2"/>WHETHER WE ARE ELICITING S 2</p>
  996. <p begin="00:37:37.07" end="00:37:40.80" region="speaker"><metadata ccrow="14" cccol="2"/>SPECIFIC ANTIBODIES AND ALSO</p>
  997. <p begin="00:37:40.80" end="00:37:42.87" region="speaker"><metadata ccrow="14" cccol="0"/>WHAT TYPES OF ANTIBODIES OR THE</p>
  998. <p begin="00:37:42.87" end="00:37:44.17" region="speaker"><metadata ccrow="14" cccol="4"/>FUNCTION WHETHER THEY&apos;RE</p>
  999. <p begin="00:37:44.17" end="00:37:48.00" region="speaker"><metadata ccrow="14" cccol="3"/>NEUTRALIZING OR OTHERWISE.</p>
  1000. <p begin="00:37:48.00" end="00:37:50.50" region="speaker"><metadata ccrow="14" cccol="0"/>WE EXPRESS CORONA VIRUS S 2P ON</p>
  1001. <p begin="00:37:50.50" end="00:37:52.00" region="speaker"><metadata ccrow="14" cccol="6"/>SURFACE OF DESIGNER</p>
  1002. <p begin="00:37:52.00" end="00:37:55.50" region="speaker"><metadata ccrow="14" cccol="1"/>NANOPARTICLES IN COLLABORATION</p>
  1003. <p begin="00:37:55.50" end="00:38:02.60" region="speaker"><metadata ccrow="14" cccol="0"/>WITH THE KING LAB, UNIVERSITY OF</p>
  1004. <p begin="00:38:02.60" end="00:38:03.17" region="speaker"><metadata ccrow="14" cccol="10"/>WASHINGTON.</p>
  1005. <p begin="00:38:03.17" end="00:38:06.67" region="speaker"><metadata ccrow="14" cccol="1"/>ALSO S THE 2P BY mRNA AND NOT</p>
  1006. <p begin="00:38:06.67" end="00:38:08.83" region="speaker"><metadata ccrow="14" cccol="1"/>JUST SOLUBLE TRIMERIC FORM BUT</p>
  1007. <p begin="00:38:08.83" end="00:38:11.13" region="speaker"><metadata ccrow="14" cccol="2"/>ALSO BY DELIVERING WITH mRNA</p>
  1008. <p begin="00:38:11.13" end="00:38:13.47" region="speaker"><metadata ccrow="14" cccol="1"/>THAT OUR S 2P ANTIGEN IS MORE</p>
  1009. <p begin="00:38:13.47" end="00:38:16.67" region="speaker"><metadata ccrow="14" cccol="2"/>IMMUNOGENIC THAN MRS S WILD</p>
  1010. <p begin="00:38:16.67" end="00:38:16.97" region="speaker"><metadata ccrow="14" cccol="13"/>TYPE.</p>
  1011. <p begin="00:38:16.97" end="00:38:18.87" region="speaker"><metadata ccrow="14" cccol="0"/>SO WITH THAT, I WILL STOP BUT I</p>
  1012. <p begin="00:38:18.87" end="00:38:21.47" region="speaker"><metadata ccrow="14" cccol="0"/>DO WANT TO THANK A LOT OF PEOPLE</p>
  1013. <p begin="00:38:21.47" end="00:38:24.50" region="speaker"><metadata ccrow="14" cccol="9"/>THAT ARE HERE.</p>
  1014. <p begin="00:38:24.50" end="00:38:25.53" region="speaker"><metadata ccrow="14" cccol="1"/>PARTICULARLY THE CORONA VIRUS</p>
  1015. <p begin="00:38:25.53" end="00:38:28.17" region="speaker"><metadata ccrow="14" cccol="5"/>TEAM AT THE VRC LED BY</p>
  1016. <p begin="00:38:28.17" end="00:38:31.73" region="speaker"><metadata ccrow="14" cccol="2"/>DR. GRAHAM AND DR. MUSCOLA,</p>
  1017. <p begin="00:38:31.73" end="00:38:33.53" region="speaker"><metadata ccrow="14" cccol="0"/>ANTIBODY IS INSTRUMENTAL IN ALL</p>
  1018. <p begin="00:38:33.53" end="00:38:37.97" region="speaker"><metadata ccrow="14" cccol="0"/>THESE PROJECTS PARTICULARLY OLU.</p>
  1019. <p begin="00:38:37.97" end="00:38:41.27" region="speaker"><metadata ccrow="14" cccol="3"/>AND THEN COLLABORATORS AND</p>
  1020. <p begin="00:38:41.27" end="00:38:42.73" region="speaker"><metadata ccrow="14" cccol="1"/>CONTRIBUTORS THAT YOU SEE ON A</p>
  1021. <p begin="00:38:42.73" end="00:38:44.53" region="speaker"><metadata ccrow="14" cccol="2"/>LOT OF THESE STUDIES, THESE</p>
  1022. <p begin="00:38:44.53" end="00:38:46.33" region="speaker"><metadata ccrow="14" cccol="0"/>WOULDN&apos;T BE POSSIBLE WITHOUT THE</p>
  1023. <p begin="00:38:46.33" end="00:38:49.73" region="speaker"><metadata ccrow="14" cccol="4"/>STRUCTURAL EXPERTISE AND</p>
  1024. <p begin="00:38:49.73" end="00:38:51.33" region="speaker"><metadata ccrow="14" cccol="4"/>NANOPARTICLE DESIGN AND</p>
  1025. <p begin="00:38:51.33" end="00:38:54.73" region="speaker"><metadata ccrow="14" cccol="3"/>ESPECIALLY FOR ELUCIDATING</p>
  1026. <p begin="00:38:54.73" end="00:38:56.47" region="speaker"><metadata ccrow="14" cccol="1"/>PROTECTION MECHANISMS TEAM AT</p>
  1027. <p begin="00:38:56.47" end="00:39:00.43" region="speaker"><metadata ccrow="14" cccol="0"/>THE UNC IN RALPH&apos;S LAB HAS BEEN</p>
  1028. <p begin="00:39:00.43" end="00:39:02.03" region="speaker"><metadata ccrow="14" cccol="3"/>PARTICULARLY INSTRUMENTAL.</p>
  1029. <p begin="00:39:02.03" end="00:39:03.07" region="speaker"><metadata ccrow="14" cccol="5"/>WITH THAT, I WILL TAKE</p>
  1030. <p begin="00:39:03.07" end="00:39:09.73" region="speaker"><metadata ccrow="14" cccol="11"/>QUESTIONS.</p>
  1031. <p begin="00:39:09.73" end="00:39:09.87" region="speaker"><metadata ccrow="14" cccol="11"/>[APPLAUSE]</p>
  1032. <p begin="00:39:09.87" end="00:39:13.03" region="speaker"><metadata ccrow="14" cccol="0"/>&gt;&gt; SO GIVEN THE HUMANS EXPRESS A</p>
  1033. <p begin="00:39:13.03" end="00:39:15.23" region="speaker"><metadata ccrow="14" cccol="0"/>FORM OF SIALIC ACID AND NOT THE</p>
  1034. <p begin="00:39:15.23" end="00:39:16.77" region="speaker"><metadata ccrow="14" cccol="5"/>G FORM OF SIALIC ACID.</p>
  1035. <p begin="00:39:16.77" end="00:39:18.80" region="speaker"><metadata ccrow="14" cccol="1"/>ARE YOU GROWING YOUR MOLECULES</p>
  1036. <p begin="00:39:18.80" end="00:39:22.30" region="speaker"><metadata ccrow="14" cccol="0"/>IN CELLS THAT HAVE BOTH A AND G?</p>
  1037. <p begin="00:39:22.30" end="00:39:24.30" region="speaker"><metadata ccrow="14" cccol="2"/>OR ARE THEY HUMAN WITH HUMAN</p>
  1038. <p begin="00:39:24.30" end="00:39:24.83" region="speaker"><metadata ccrow="14" cccol="13"/>SERUM?</p>
  1039. <p begin="00:39:24.83" end="00:39:28.10" region="speaker"><metadata ccrow="14" cccol="5"/>&gt;&gt; SO THESE -- ALL THE</p>
  1040. <p begin="00:39:28.10" end="00:39:29.37" region="speaker"><metadata ccrow="14" cccol="1"/>CONSTRUCTS THAT WE HAVE SO FAR</p>
  1041. <p begin="00:39:29.37" end="00:39:32.10" region="speaker"><metadata ccrow="14" cccol="0"/>HAVE BEEN EXPRESSED IN MAMMALIAN</p>
  1042. <p begin="00:39:32.10" end="00:39:32.50" region="speaker"><metadata ccrow="14" cccol="10"/>CELL LINES.</p>
  1043. <p begin="00:39:32.50" end="00:39:34.90" region="speaker"><metadata ccrow="14" cccol="6"/>&gt;&gt; MAMMALS OR HUMAN?</p>
  1044. <p begin="00:39:34.90" end="00:39:38.07" region="speaker"><metadata ccrow="14" cccol="7"/>&gt;&gt; JUST 293 CELLS.</p>
  1045. <p begin="00:39:38.07" end="00:39:40.37" region="speaker"><metadata ccrow="14" cccol="2"/>&gt;&gt; IS THAT A MOUSE, A HUMAN?</p>
  1046. <p begin="00:39:40.37" end="00:39:43.33" region="speaker"><metadata ccrow="14" cccol="1"/>&gt;&gt; I THINK IT&apos;S A HUMAN CELL.</p>
  1047. <p begin="00:39:43.33" end="00:39:44.70" region="speaker"><metadata ccrow="14" cccol="11"/>&gt;&gt; HUMAN.</p>
  1048. <p begin="00:39:44.70" end="00:39:46.37" region="speaker"><metadata ccrow="14" cccol="6"/>AND IN HUMAN SERUM.</p>
  1049. <p begin="00:39:46.37" end="00:39:48.33" region="speaker"><metadata ccrow="14" cccol="1"/>&gt;&gt; ALL SERUM THAT WE HAVE BEEN</p>
  1050. <p begin="00:39:48.33" end="00:39:49.70" region="speaker"><metadata ccrow="14" cccol="1"/>TESTING HAVE BEEN MOUSE SERUM.</p>
  1051. <p begin="00:39:49.70" end="00:39:53.17" region="speaker"><metadata ccrow="14" cccol="1"/>&gt;&gt; SO MOUSE SG, NOT ONLY THAT</p>
  1052. <p begin="00:39:53.17" end="00:39:56.47" region="speaker"><metadata ccrow="14" cccol="3"/>SERUM YOU ARE TESTING, I&apos;M</p>
  1053. <p begin="00:39:56.47" end="00:39:57.53" region="speaker"><metadata ccrow="14" cccol="2"/>WONDERING IF -- (OVERLAPPING</p>
  1054. <p begin="00:39:57.53" end="00:39:59.00" region="speaker"><metadata ccrow="14" cccol="11"/>SPEAKERS)</p>
  1055. <p begin="00:39:59.00" end="00:40:00.70" region="speaker"><metadata ccrow="14" cccol="0"/>&gt;&gt; BINDS THE A FORM AND NOT THE</p>
  1056. <p begin="00:40:00.70" end="00:40:02.10" region="speaker"><metadata ccrow="14" cccol="1"/>G FORM, IT MAKES A DIFFERENCE</p>
  1057. <p begin="00:40:02.10" end="00:40:03.20" region="speaker"><metadata ccrow="14" cccol="0"/>HOW YOU IMMUNIZE WHETHER YOU&apos;RE</p>
  1058. <p begin="00:40:03.20" end="00:40:05.00" region="speaker"><metadata ccrow="14" cccol="3"/>GOING TO GET ANTIBODIES TO</p>
  1059. <p begin="00:40:05.00" end="00:40:06.07" region="speaker"><metadata ccrow="14" cccol="3"/>SOMETHING THAT BLOCKS THAT</p>
  1060. <p begin="00:40:06.07" end="00:40:06.70" region="speaker"><metadata ccrow="14" cccol="8"/>BINDING OR NOT.</p>
  1061. <p begin="00:40:06.70" end="00:40:08.37" region="speaker"><metadata ccrow="14" cccol="1"/>&gt;&gt; SO THE NEUTRALIZATION ASSAY</p>
  1062. <p begin="00:40:08.37" end="00:40:10.40" region="speaker"><metadata ccrow="14" cccol="0"/>WE ARE DOING THAT WOULD -- IF IT</p>
  1063. <p begin="00:40:10.40" end="00:40:12.77" region="speaker"><metadata ccrow="14" cccol="0"/>WERE TO PICK UP ANY SIALIC ACID</p>
  1064. <p begin="00:40:12.77" end="00:40:16.67" region="speaker"><metadata ccrow="14" cccol="0"/>BINDING, IS DONE IN A HUMAN CELL</p>
  1065. <p begin="00:40:16.67" end="00:40:18.57" region="speaker"><metadata ccrow="14" cccol="6"/>LINE, HUH CELL LINE.</p>
  1066. <p begin="00:40:18.57" end="00:40:20.37" region="speaker"><metadata ccrow="14" cccol="7"/>&gt;&gt; IN HUMAN SERUM.</p>
  1067. <p begin="00:40:20.37" end="00:40:22.67" region="speaker"><metadata ccrow="14" cccol="1"/>&gt;&gt; WE HAVE TESTED HUMAN SERUM</p>
  1068. <p begin="00:40:22.67" end="00:40:23.80" region="speaker"><metadata ccrow="14" cccol="3"/>ALSO AND ALSO MOUSE SERUM.</p>
  1069. <p begin="00:40:23.80" end="00:40:25.53" region="speaker"><metadata ccrow="14" cccol="3"/>&gt;&gt; WHAT DO YOU GROW IT IN?</p>
  1070. <p begin="00:40:25.53" end="00:40:27.07" region="speaker"><metadata ccrow="14" cccol="9"/>THE CELL LINE?</p>
  1071. <p begin="00:40:27.07" end="00:40:32.03" region="speaker"><metadata ccrow="14" cccol="2"/>&gt;&gt; THE CELL LINE IS GROWN IN</p>
  1072. <p begin="00:40:32.03" end="00:40:32.53" region="speaker"><metadata ccrow="14" cccol="8"/>FETAL CAT SERUM.</p>
  1073. <p begin="00:40:32.53" end="00:40:34.17" region="speaker"><metadata ccrow="14" cccol="0"/>&gt;&gt; IT&apos;S GOING TO HAVE G AND NOT</p>
  1074. <p begin="00:40:34.17" end="00:40:36.17" region="speaker"><metadata ccrow="14" cccol="0"/>THE SAME WHAT A REAL HUMAN CELL</p>
  1075. <p begin="00:40:36.17" end="00:40:36.80" region="speaker"><metadata ccrow="14" cccol="11"/>WILL HAVE.</p>
  1076. <p begin="00:40:36.80" end="00:40:38.60" region="speaker"><metadata ccrow="14" cccol="1"/>SO YOU MAY JUST WANT TO THINK</p>
  1077. <p begin="00:40:38.60" end="00:40:40.47" region="speaker"><metadata ccrow="14" cccol="0"/>ABOUT GROWING IT IN HUMAN SERUM.</p>
  1078. <p begin="00:40:40.47" end="00:40:42.03" region="speaker"><metadata ccrow="14" cccol="2"/>&gt;&gt; WE WILL THINK ABOUT DOING</p>
  1079. <p begin="00:40:42.03" end="00:40:42.97" region="speaker"><metadata ccrow="14" cccol="1"/>THAT BUT I DON&apos;T THINK THAT IF</p>
  1080. <p begin="00:40:42.97" end="00:40:46.07" region="speaker"><metadata ccrow="14" cccol="2"/>WE WANTED TO TEST ANY SIALIC</p>
  1081. <p begin="00:40:46.07" end="00:40:48.13" region="speaker"><metadata ccrow="14" cccol="2"/>ACID FUNCTIONALITY FOR THESE</p>
  1082. <p begin="00:40:48.13" end="00:40:49.13" region="speaker"><metadata ccrow="14" cccol="1"/>ANTIBODIES WE HAVE TO BE VERY</p>
  1083. <p begin="00:40:49.13" end="00:40:50.13" region="speaker"><metadata ccrow="14" cccol="0"/>PARTICULAR JUST IN GENERAL, NOT</p>
  1084. <p begin="00:40:50.13" end="00:40:51.47" region="speaker"><metadata ccrow="14" cccol="0"/>JUST WITH THE TYPES OF CELLS WE</p>
  1085. <p begin="00:40:51.47" end="00:40:52.97" region="speaker"><metadata ccrow="14" cccol="10"/>ARE GROWING.</p>
  1086. <p begin="00:40:52.97" end="00:40:55.63" region="speaker"><metadata ccrow="14" cccol="7"/>SO PEOPLE -- YEAH.</p>
  1087. <p begin="00:40:55.63" end="00:41:03.10" region="speaker"><metadata ccrow="14" cccol="0"/>SO THE SIALIC ACID BINDING STORY</p>
  1088. <p begin="00:41:03.10" end="00:41:05.30" region="speaker"><metadata ccrow="14" cccol="0"/>SO TO SPEAK HAS BEEN COMING OUT</p>
  1089. <p begin="00:41:05.30" end="00:41:05.83" region="speaker"><metadata ccrow="14" cccol="11"/>RECENTLY.</p>
  1090. <p begin="00:41:05.83" end="00:41:07.10" region="speaker"><metadata ccrow="14" cccol="2"/>SO HIS LAB PUBLISHED A SPIKE</p>
  1091. <p begin="00:41:07.10" end="00:41:14.63" region="speaker"><metadata ccrow="14" cccol="0"/>BOUND TO SIALIC ACID ON SURFACE</p>
  1092. <p begin="00:41:14.63" end="00:41:16.23" region="speaker"><metadata ccrow="14" cccol="0"/>UNDERSTANDS HOW SIALIC ACID, THE</p>
  1093. <p begin="00:41:16.23" end="00:41:18.97" region="speaker"><metadata ccrow="14" cccol="0"/>ROLE OF IT PLAYS WITH MRS CORONA</p>
  1094. <p begin="00:41:18.97" end="00:41:35.83" region="speaker"><metadata ccrow="14" cccol="1"/>VIRUS PATHOGENESIS IN GENERAL.</p>
  1095. <p begin="00:41:35.83" end="00:41:41.40" region="speaker"><metadata ccrow="14" cccol="6"/>ANY MORE QUESTIONS?</p>
  1096. <p begin="00:41:41.40" end="00:41:48.20" region="speaker"><metadata ccrow="14" cccol="11"/>THANK YOU.</p>
  1097. <p begin="00:41:48.20" end="00:43:11.43" region="speaker"><metadata ccrow="14" cccol="11"/>[APPLAUSE]</p>
  1098. </div>
  1099. </body>
  1100. </tt>
  1101.  
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