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Influenza Vaccine Responses

Influenza Vaccine Responses. Zhiping Ye, M.D., Ph.D. Division of Viral Products OVRR/CBER/FDA. Prepared for Vaccines and Related Biological Products Advisory Committee 25 February 2011.

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Influenza Vaccine Responses

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  1. Influenza Vaccine Responses Zhiping Ye, M.D., Ph.D. Division of Viral Products OVRR/CBER/FDA Prepared for Vaccines and Related Biological Products Advisory Committee 25 February 2011

  2. Recent A(H1N1)pdm09, A(H3N2) and B isolates were analyzed by using 12 panels of sera from adults, elderly and pediatric populations receiving seasonal trivalent inactivated vaccine (2010-2011 formulation). Sera were analyzed for the presence of antibodies to the HA antigens of recent virus isolates Hemagglutination inhibition (HI) titers for recent isolates were compared to HI titer of the vaccine virus by HI assay A subset of sera were tested by micro-neutralization assay Inactivated Vaccine Serology Studies 2

  3. AUSTRALIA ADULTS OLDER ADULTS A/California/7/2009 (H1N1pdm) (NYMC X-179A)A/Victoria/210/2009 (H3N2) (NYMC X-187)B/Brisbane/60/2008 A/California/7/2009 (H1N1pdm) (NYMC X-179A)A/Victoria/210/2009 (H3N2) (NYMC X-187)B/Brisbane/60/2008 CHINA CHILDREN ADULTS OLDER ADULTS EUROPE ADULTS OLDER ADULTS A/California/7/2009 (H1N1pdm) (NYMC X-181)A/Victoria/210/2009 (H3N2) (NYMC X-187)B/Brisbane/60/2008 BX-35 A/California/7/2009 (H1N1pdm) (NYMC X-179A)A/Victoria/210/2009 (H3N2) (NYMC X-187)B/Brisbane/60/2008 JAPAN ADULTS OLDER ADULTS USA CHILDREN ADULTS OLDER ADULTS A/California/7/2009 (H1N1pdm) (NYMC X-179A)A/Victoria/210/2009 (H3N2) (NYMC X-187)B/Brisbane/60/2008 3 Serum panels used for studies:seasonal trivalent vaccine 

  4. A(H1N1)pdm09 Virus 4

  5. This slide shows the antigenic map generated from HI data using ferret sera and H1N1 viruses. Viruses are represented as circles, antisera as squares. Vaccine strain are represented by the larger dot, other strains are coloured by antigenic cluster. Grid indicates 1 unit of antigenic distance, a 2-fold dilution in HI titer. 5 Antigenic cartography of A(H1N1)pdm09 isolates

  6. Antigens for serology:pandemic A(H1N1) 2011 VACCINE VIRUSES A/California/07/2009 (wt, X-179A and X-181) REPRESENTATIVE CURRENT VIRUSES • A/Christchurch/16/2010n125d, d94n v250a • A/Kentucky/9/2010* g155e • A/Milano/3/2010 (MDCK cell) • A/Brisbane/10/2010 n125d • A/Wisconsin/08/2010 s183p • A/Sichuan/SWL-1/2009 l32i • A/Shanghai-Changning/SWL1700/2010 e374k q223r • A/Victoria/663/2010 • A/Perth/219/2010 s185t, s451n • A/Sri Lanka/21/2010 • A/Brisbane/59/2007 [former seasonal A(H1N1)] 6

  7. HI ANTIBODY RESPONSES TO THE PANDEMIC A(H1N1) 2010-11 COMPONENT (% GMT) This slide summarizes average geometric mean antibody titers of vaccine trials by HI test, indicating that A/California/7/09 antigen stimulated antibodies of similar titers to the vaccine and recent H1N1 viruses. relative GMT 7

  8. A(H3N2) Virus 8

  9. Summary of A(H3N2) cartography A Green=Vic/208 clade This slide shows the antigenic map generated from HI data using ferret sera and H3N2 viruses. Viruses are represented as circles, antisera as squares. Vaccine strains are represented by the larger dots, other strains are coloured by antigenic cluster. Grid indicates 1 unit of antigenic distance, a 2-fold dilution in HI titer. 9

  10. Antigens for serology:A (H3N2) 2011 VACCINE VIRUSES A/Perth/16/2009-like (wt and X-187) REPRESENTATIVE CURRENT VIRUSES A/Rhode Island/1/2010 d53n, y94h, i230v, e280a A/Victoria/563/2010d53n, y94h, i230v, e280a A/Perth/10/2010d53n, y94h, i230v, e280a A/Wisconsin/13/2010i260m, r261q, p162s A/Brisbane/11/2010 l194p A/Hong Kong/3170/2010i260m, r261q, p162s A/Fujian-Tong’an/196/2009 A/Shanghai-Luwan/1466/2010*d53n, y94h, t212a, i230v, e280a A/Brisbane/220/2010 d53n, y94h, i230v, e280a A/Kobe/357/2010 (MDCK cell)* d53n,y94y,230v A/Okinawa/72/2010 (MDCK cell)* d53n,y94y,230v A/Yokohama/96/2010 (MDCK cell) d53n,y94y,230v 10

  11. HI ANTIBODY RESPONSES TO THE A(H3N2) COMPONENT (% GMT) This slide summarizes average geometric mean antibody titers of vaccine trials by HI test, indicating that A/Perth/16/2009-like HA antigen stimulated antibodies of similar titers to the vaccine and recent H3N2 viruses. % GMT 11

  12. Influenza B Virus 12

  13. Antigenic cartography of B/Victoria viruses (Cambridge University) This slide shows the antigenic map generated from HI data using ferret sera and B viruses. Viruses are represented as circles, antisera as squares. Vaccine strains are represented by the larger dots, other strains are coloured by antigenic cluster. Grid indicates 1 unit of antigenic distance, a 2-fold dilution in HI titer. B/Singapore/616/2008 13

  14. Antigenic cartography of B/Yamagata viruses (Cambridge University) This slide shows the antigenic map generated from HI data using ferret sera and B viruses. Viruses are represented as circles, antisera as squares. Vaccine strains are represented by the larger dots, other strains are coloured by antigenic cluster. Grid indicates 1 unit of antigenic distance, a 2-fold dilution in HI titer. 14

  15. Antigens for serology:B 2011 VACCINE VIRUS B/Brisbane/60/2008 REPRESENTATIVE CURRENT VIRUSES B/Singapore/616/2008* clade 6 B/Bolivia/1526/2010* clade 6 B/Georgia/28/2010* clade 1 B/Genoa/2/2010 B/Hunan-Yuhua/1930/2010 clade 1 B/Heilongjiang-Hulan/116/2010clade 1 B/Victoria/506/2010 clade 1 B/Hiroshima/9/2010 (egg or cell) clade 1 • B/Florida/4/2006 • B/Wisconsin/1/2010 • B/Hubei Wujiagang/158/2009 • B/England/110/2010 • B/Washington/1/2010 • B/Guangdong-Luohu/1512/2010 • B/Fujian Gulou/1272/2008 15

  16. HI ANTIBODY RESPONSES TO THE B COMPONENT (% GMT) This slide summarizes average geometric mean antibody titers of vaccine trials by HI test, indicating that B/Brisbine/60/2008 HA antigen stimulated antibodies of similar titers to the vaccine and recent B/Vic/2/87 lineage viruses, but titers were lower to recent B/Yamagate/16/88 lineage viruses. % GMT 16

  17. Conclusions • H1N1 • Representative recent pandemic A(H1N1) viruses were covered by vaccine containing A/California/07/2009 • H3N2 • Representative recent (H3N2) viruses were covered by vaccine containing A/Perth/16/2009-like vaccines • B • B/VICTORIA/2/87-lineage • Representative recent viruses were well covered by current vaccine • B/YAMAGATA/16/88-lineage • Representative recent viruses were less well covered by current vaccine 17

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