influenza vaccine responses zhiping ye, m.d., ph.d. division of viral products ovrr/cber/fda...
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Influenza Vaccine Responses
Zhiping Ye, M.D., Ph.D.
Division of Viral Products
OVRR/CBER/FDA
Prepared for Vaccines and Related Biological
Products Advisory Committee28 February 2012
Inactivated Vaccine Serology Studies
Recent A(H1N1)pdm09, A(H3N2) and B isolates were analyzed by using 5 panels of sera from adults, 5 panels from elderly and 2 panels from pediatric populations receiving seasonal trivalent inactivated vaccine (2011-2012 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
2
Serum panels used for studies:
seasonal trivalent vaccine AUSTRALIA
A/California/7/2009 (H1N1pdm09) (NYMC X-181) A/Victoria/210/2009 (H3N2) (NYMC X-187) B/Brisbane/60/2008 (Victoria lineage)
CHINA
EUROPE
JAPAN
USA
ADULTS
OLDER ADULTS
CHILDREN (12-60 Mon))
ADULTS
OLDER ADULTS
ADULTS
OLDER ADULTS
ADULTS
OLDER ADULTS
CHILDREN (6-24 Mon)
ADULTS
OLDER ADULTS
A/California/7/2009 (H1N1pdm09)-like A/Victoria/210/2009 (H3N2)-like B/Brisbane/60/2008 (Victoria lineage)
A/California/7/2009 (H1N1pdm09) (NYMC X-181) A/Victoria/210/2009 (H3N2) (NYMC X-187) B/Brisbane/60/2008 (Victoria lineage)
A/California/7/2009 (H1N1pdm09) (NYMC X-179A) A/Victoria/210/2009 (H3N2) (NYMC X-187) B/Brisbane/60/2008 (Victoria lineage)
A/California/7/2009 (H1N1pdm09) (NYMC X-179A) A/Victoria/210/2009 (H3N2) (NYMC X-187) B/Brisbane/60/2008 (Victoria lineage)
Antigens for serology: A(H1N1)pdm09
VACCINE VIRUS
A/California/7/2009-likeREPRESENTATIVE CURRENT VIRUSES• A/Cape Town/60/2011• A/Valparaiso/17275/2011 • A/Wisconsin/26/2011 cell• A/Perth/533/2011 • A/St. Petersburg/100/2011• A/Argentina/656/2011 cell• A/Florida/27/2011
HI ANTIBODY RESPONSES TO THE A(H1N1)pdm09 COMPONENT
(% GMT)–Example: Older Adults
Trial No. of Sera
Virus strain pre-vaccGMT
Post-vacc GMT
Post-vacc GMT
reduction )%(
Older Adults
EU
24 A/California/7/2009 5 34
A/St. Petersburg/100/2011 5 17 50
A/Cape Town/60/2011 5 24 29
A/Valparaiso/17217275.2011 5 26 24
A/Aigentina/656/2011 5 8 76
Older Adults
US
24 A/California/7/2009 7 45
A/St. Petersburg/100/2011 5 18 60
A/Cape Town/60/2011 7 42 7
A/Valparaiso/17217275.2011 6 35 22
A/Aigentina/656/2011 5 11 76
Data from CBER
HI ANTIBODY RESPONSES TO THE A(H1N1)pdm09 COMPONENT – SUMMARY OF
DATA FROM ALL LABORATORIESre
lativ
e G
MT
Antigens for serology:A(H3N2)
VACCINE VIRUS
A/Perth/16/2009-like
REPRESENTATIVE CURRENT VIRUSES• A/Victoria/361/2011 egg; group 3• A/Hunan-Yueyanglou/1320/2011 cell; group 3• A/Hunan-Suxian/1319/2011 cell; group 3• A/Utah/12/2011 cell; group 3• A/Chiang Rai/277/2011 cell; group 3• A/Kobe/241/2011 cell; group 3• A/Bangladesh/5071/2011 cell; group 3• A/South Australia/03/2011 cell; group 3
• A/Guangdong-Jinping/1334/2011 cell; group 6• A/Brisbane/299/2011 egg; group 6• A/Christchurch/28/2011 egg; group 6• A/Kentucky/5/2011 cell; group 6• A/Victoria/362/2011 egg; group 6
HI ANTIBODY RESPONSES TO THE A(H3N2) COMPONENT –Example: Older
AdultsTrial No. of
Sera
Virus strain pre-vaccGM
T
Post-vacc GMT
Post-vacc GMT
reduction )%(
Older Adults
China
30 A/Victoria/210/2009 19 70A/Brisbane/299/2011 12 47 33
A/Christchurch/28/2011 32 130 0
A/Kentucky/5/2011 7 9 87A/Victoria/361/2011 10 26 63A/Victoria/362/2011 12 35 50
All viruses 47Older Adults
Australia
20 A/Victoria/210/2009 8 46A/Brisbane/299/2011 6 35 24
A/Christchurch/28/2011 6 27 41
A/Kentucky/5/2011 5 7 85A/Victoria/361/2011 5 13 72A/Victoria/362/2011 7 29 37
All viruses 52
Data from NIBSC
HI ANTIBODY RESPONSES TO THE A(H3N2) COMPONENT – SUMMARY OF DATA FROM ALL
LABORATORIES
rela
tive
GM
T
HI ANTIBODY RESPONSES TO THE A(H3N2) COMPONENT –GMT ratio plots
Data from NIBSC
H3N2 - A/Victoria/361/11Unadjusted GMT Ratios with Confidence Limits
Reference strain A/Victoria/210/09
country AU CH JP UK US
GM
T R
atio
0.062
0.125
0.25
0.5
1
2
4
8
16
Panel
AU_A AU_E CH_A CH_E CH_P JP_A JP_E UK_A UK_E US_A US_E
H3N2 - A/Kentucky/5/11Unadjusted GMT Ratios with Confidence Limits
Reference strain A/Victoria/210/09
country AU CH JP UK US
GM
T R
atio
0.062
0.125
0.25
0.5
1
2
4
8
16
Panel
AU_A AU_E CH_A CH_E CH_P JP_A JP_E UK_A UK_E US_A US_E
H3N2 - A/Brisbane/299/11Unadjusted GMT Ratios with Confidence Limits
Reference strain A/Victoria/210/09
country AU CH JP UK US
GM
T R
atio
0.062
0.125
0.25
0.5
1
2
4
8
16
Panel
AU_A AU_E CH_A CH_E CH_P JP_A JP_E UK_A UK_E US_A US_E
H3N2 - A/Victoria/362/11Unadjusted GMT Ratios with Confidence Limits
Reference strain A/Victoria/210/09
country AU CH JP UK US
GM
T R
atio
0.062
0.125
0.25
0.5
1
2
4
8
16
Panel
AU_A AU_E CH_A CH_E CH_P JP_A JP_E UK_A UK_E US_A US_E
Antigens for serology:B
VACCINE VIRUS
B/Brisbane/60/2008 (Vic-lineage) REPRESENTATIVE CURRENT VIRUSES Vic-lineage
• B/Dominican Republic/5486/2011• B/Hong Kong/767/2011• B/Nevada/3/2011• B/Shanghai-Chongming/1458/2011• B/Chongqing-Yuzhong/1651/2011• B/Cameroon/11V-12080GVF1/2011• B/Tokyo/91107/2011
Yamagata-lineage
• B/Wisconsin/1/2010• B/Texas/6/2011• B/Jiangsu-Tianning/1470/2011
HI ANTIBODY RESPONSES TO THE B COMPONENT –Example: Younger Adults
Data from CDC
Population N Antigen Pre GMT Post GMT
AUSTRALIA 24 B/BRISBANE/60/2008 30 110
24 B/NEVADA/03/2011 22 80
24 B/DOMINICAN REPUBLIC/5486/2011 42 143
23 B/CHONGQING-YUZHONG/1651/2011 37 165
23 B/WISCONSIN/1/2010 22 41
US 24 B/BRISBANE/60/2008 26 196
24 B/NEVADA/03/2011 19 147
24 B/DOMINICAN REPUBLIC/5486/2011 44 277
24 B/CHONGQING-YUZHONG/1651/2011 44 311
24 B/WISCONSIN/1/2010 22 113
JAPAN 29 B/BRISBANE/60/2008 29 42
30 B/NEVADA/03/2011 17 27
30 B/DOMINICAN REPUBLIC/5486/2011 38 62
30 B/CHONGQING-YUZHONG/1651/2011 50 73
30 B/WISCONSIN/1/2010 33 37
HI ANTIBODY RESPONSES TO THE B COMPONENT - SUMMARY OF DATA FROM ALL LABORATORIES
rela
tive
GM
T
Summary H1N1pdm09
– Representative recent A(H1N1)pdm09 viruses were covered by vaccine containing A/California/7/2009
H3N2– Many representative recent (H3N2) viruses showed
significant reductions in GMT when tested with sera from recipients of vaccine containing A/Perth/16/2009-like viruses
B– B/VICTORIA/2/87-lineage
• Representative recent viruses were well covered by current vaccine (B/Brisbane/60/2008)
– B/YAMAGATA/16/88-lineage• Representative recent viruses were less well covered by the latest
vaccine (B/Florida/4/2006-like viruses, 2008/2009 influenza season)