Division of Bacterial, Parasitic and Allergenic Products OVRR/CBER/FDA
Influenza Vaccine Responses Zhiping Ye, M.D., Ph.D. Division of Viral Products OVRR/CBER/FDA...
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WHO SARS Coordination and Response GLOBAL HEALTH SECURITY KS 13/11/0 WHO Global Influenza Programme GLOBAL HEALTH SECURITY text 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 18 February 2009
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Transcript of Influenza Vaccine Responses Zhiping Ye, M.D., Ph.D. Division of Viral Products OVRR/CBER/FDA...
Influenza Vaccine Responses
Zhiping Ye, M.D., Ph.D.
Division of Viral Products
OVRR/CBER/FDA
Prepared for Vaccines and Related Biological
Products Advisory Committee18 February 2009
Serum Panels Used for Serology
• AUSTRALIA, IAN BARR, PH.D. ADULTS A/Solomon Islands IVR-145 (H1N1) • WHO, AUSTRALIA ELDERLY A/Uruguay/716/2007 NYMC X175C(H3N2) • B/Florida/4/2006 • EUROPE, JOHN WOOD, PH.D. ADULTS A/Brisbane/59/2007 IVR-148 (H1N1) • NIBSC, ENGLAND ELDERLY A/Uruguay/716/2007 NYMC X175C(H3N2)• B/Florida/4/2006 • JAPAN, TAKATO ODIGARI, PH.D. ADULTS A/Brisbane/59/2007 IVR-148 (H1N1) )• NIID, JAPAN ELDERLY A/Uruguay/716/2007 NYMC
X175C(H3N2) • B/Florida/4/2006• USA, STEFAN GRAVENSTEIN, M.D. ADULTS A/Brisbane/59/2007 IVR-148 (H1N1) • EASTERN VIRGINIA ELDERLY A/Uruguay/716/2007 NYMC X175C(H3N2) • MEDICAL SCHOOL PEDIATRIC B/Florida/4/2006
Antigens for Serology (H1N1)
8
VACCINE STRAINA/BRISBANE/59/2007 2BREPRESENTATIVE CURRENT STRAINS
• A/Brazil/5943/2008 2B• A/England/412/2008 2B• A/Hiroshima/48/2008-E 2B• A/Hiroshima/48/2008-C 2B• A/Pennsylvania/8/2008 2B• A/Victoria/501/2008 2B
• A/Hong Kong/1870/2008-E 2C• A/Hong Kong/1870/2008-C 2C • A/Guam/1/2007 2C• A/Shiga/8/2008 2C • A/Perth/200/2008 2C
HI ANTIBODY RESPONSES TO THE H1N1 ADULT POPULATION (NIBSC)
3
N Antigen % RisePre-vaccGMT
Post-vaccGMT
Pre-vacc % HI>40
Post- vacc % HI>40
EU 24 A/Brisbane/59/07 83 9 150 17 92
24 A/Brazil/5943/2008 2B 71 7 93 8 79
24 A/England/412/2008 2B 83 8 103 8 83
24 A/Hiroshima/48/2008-C 2B 79 7 83 4 88
24 A/Hiroshima/48/2008-E 2B 83 6 74 4 83
24 A/Hong Kong/1870/2008 2C 83 7 95 4 88
24 A/Pennsylvania/8/2008 2B 67 6 50 4 71
USA 24 A/Brisbane/59/07 31 15 50 38 63
24 A/Brazil/5943/2008 2B 31 12 28 31 63
24 A/England/412/2008 2B 38 12 34 25 63
24 A/Hiroshima/48/2008-C 2B 25 11 30 25 56
24 A/Hiroshima/48/2008-E 2B 38 7 18 0 44
24 A/Hong Kong/1870/2008 2C 25 11 35 31 56
24 A/Pennsylvania/8/2008 2B 13 10 22 6 50
JP 24 A/Brisbane/59/07 29 22 61 46 75
24 A/Brazil/5943/2008 2B 17 10 21 21 42
24 A/England/412/2008 2B 17 10 25 8 46
24 A/Hiroshima/48/2008-C 2B 21 8 19 13 38
24 A/Hiroshima/48/2008-E 2B 21 7 15 13 29
24 A/Hong Kong/1870/2008 2C 25 8 19 13 33
24 A/Pennsylvania/8/2008 2B 13 6 11 4 21
HI ANTIBODY RESPONSES TO THE H1N1 Elderly POPULATION (NIBSC)
3
N Antigen % RisePre-vaccGMT
Post-vaccGMT
Pre-vacc % HI>40
Post- vacc %
HI>40
EU 24 A/Brisbane/59/07 58 11 56 17 79
24 A/Brazil/5943/2008 2B 42 9 35 17 54
24 A/England/412/2008 2B 42 13 53 25 75
24 A/Hiroshima/48/2008-C 2B 50 11 46 17 79
24 A/Hiroshima/48/2008-E 2B 46 9 36 17 67
24 A/Hong Kong/1870/2008 2C 46 11 47 21 71
24 A/Pennsylvania/8/2008 2B 29 15 42 21 71
USA 24 A/Brisbane/59/07 33 10 29 21 50
24 A/Brazil/5943/2008 2B 17 8 15 13 29
24 A/England/412/2008 2B 21 10 24 8 46
24 A/Hiroshima/48/2008-C 2B 13 8 18 4 29
24 A/Hiroshima/48/2008-E 2B 8 6 9 4 13
24 A/Hong Kong/1870/2008 2C 17 8 17 4 21
24 A/Pennsylvania/8/2008 2B 4 9 15 17 29
JP 24 A/Brisbane/59/07 33 10 28 13 50
24 A/Brazil/5943/2008 2B 17 6 12 4 21
24 A/England/412/2008 2B 38 11 39 21 67
24 A/Hiroshima/48/2008-C 2B 33 8 24 4 50
24 A/Hiroshima/48/2008-E 2B 17 7 15 8 21
24 A/Hong Kong/1870/2008 2C 33 8 25 13 46
24 A/Pennsylvania/8/2008 2B 21 9 17 17 38
A/Brisbane/59/2007 Vaccine
SUMMARY TABLEVIRUSES WITH
> 50% GMT REDUCTION
(Adults)
7
VIRUSES CBER CDC NIBSC AUS NIID TOTAL Total % REDUCED
A/Brazil/5943/2008 2B 3/3 1/3 4/6 58 (38-75)A/England/412/2008 2B 1/3 1/3 41 (31-59)A/Hiroshima/48/2008-C 2B 1/3 3/3 4/6 61 (40-80)A/Hiroshima/48/2008-E 2B 3/3 3/3 3/3 9/9 65 (51-75)A/Pennsylvania/8/2008 2B 1/3 3/3 4/6 55 (31-82)A/Victoria/501/2008 2B 3/3 2/3 5/6 64 (46-73)
A/Hong Kong/1870/2008-E 2C 3/3 1/3 1/3 3/3 3/3 11/15 57 (14-77)A/Hong Kong/1870/2008-C 2C 0/3 0/3 15 (0-33)A/Guam/1/2007 2C 0/3 0/3 18 (0-30)A/Shiga/8/2008 2C 3/3 3/3 6/6 78 (69-84)A/Perth/200/2008 2C 1/3 1/3 39 (27-52)
45/69 56 (0-84)
A/Brisbane/59/2007 Vaccine
SUMMARY TABLEVIRUSES WITH
> 50% GMT REDUCTION
(Elderly)
6
VIRUSES CBER CDC NIBSC AUS NIID TOTAL Total % REDUCED
A/Brazil/5943/2008 2B 2/3 1/3 3/6 53 (36-72)A/England/412/2008 2B 1/3 1/3 41 (31-59)A/Hiroshima/48/2008-C 2B 1/3 2/3 3/6 45 (0-69)A/Hiroshima/48/2008-E 2B 3/3 3/3 1/3 7/9 55 (40-75)A/Pennsylvania/8/2008 2B 0/3 3/3 3/6 37 (0-82)A/Victoria/501/2008 2B 3/3 0/3 3/6 41 (5-71)
A/Hong Kong/1870/2008-E 2C 2/3 0/3 1/3 1/3 3/3 7/15 42 (6-69)A/Hong Kong/1870/2008-C 2C 0/3 0/3 5 (0-15)A/Guam/1/2007 2C 0/3 0/3 0A/Shiga/8/2008 2C 3/3 3/3 6/6 71 (62-85)A/Perth/200/2008 2C 0/3 0/3 16 (0-23)
33/66 42 (0-82)
A/Brisbane/59/2007 VaccineSUMMARY TABLEVIRUSES WITH
> 50% GMT REDUCTION
(Pediatric)
7
VIRUSES CBER CDC TOTAL Total % REDUCED
A/Brazil/5943/2008 2B 1/1 1/1 71A/Pennsylvania/8/2008 2B 1/2 1/2 43 (32-53)A/Victoria/501/2008 2B 1/1 1/1 83
A/Hong Kong/1870/2008 2C 1/1 0/2 1/3 41 (23-73)A/Hong Kong/1870/2008-C 2C 0/1 0/1 37A/Shiga/8/2008 2C 1/1 1/1 90A/Perth/200/2008 2C 0/2 0/2 36 (31-40)
5/11 51 (23-83)
Antigens for Serology (H3N2)
2
VACCINE STRAIN
A/Brisbane/10/2007
A/Uruguay/716/2007
REPRESENTATIVE CURRENT STRAINS
A/BRISBANE/24/2008
A/Missouri/5/2008
A/Norway/2118/2008
A/Taiwan/471/2008
A/New York/09/2008
A/Tennessee/04/2008
A/Kanagawa/65/2008
HI ANTIBODY RESPONSES TO THE H3N2
ADULT POPULATION (CBER)
Population N Antigen % Rise
Pre-vaccGMT
Post-vaccGMT
Pre-vacc % HI>40
Post- vacc % HI>40
EU 24 A/Brisbane/10/2007 88 6 95 0 92
24 A/Uruguay/716/2007 92 6 113 4 83
24 A/Brisbane/24/2008 79 6 76 4 79
24 A/Missouri/5/2008 71 7 45 8 63
24 A/Taiwan/471/2008 67 6 35 4 71
JP 24 A/Brisbane/10/2007 54 6 25 4 54
24 A/Uruguay/716/2007 42 6 19 4 42
24 A/Brisbane/24/2008 42 7 22 8 50
24 A/Missouri/5/2008 21 5 10 4 25
24 A/Taiwan/471/2008 25 7 17 13 46
USA 24 A/Brisbane/10/2007 58 12 58 29 83
24 A/Uruguay/716/2007 75 16 95 38 83
24 A/Brisbane/24/2008 75 15 90 38 88
24 A/Missouri/5/2008 38 18 52 46 79
24 A/Taiwan/471/2008 54 14 40 29 75
9
HI ANTIBODY RESPONSES TO THE H3N2
Elderly POPULATION (CBER)
Population N Antigen % Rise
Pre-vaccGMT
Post-vaccGMT
Pre-vacc % HI>40
Post- vacc % HI>40
EU 24 A/Brisbane/10/2007 79 8 101 13 88
24 A/Uruguay/716/2007 79 12 113 29 88
24 A/Brisbane/24/2008 75 12 98 25 79
24 A/Missouri/5/2008 58 9 45 17 63
24 A/Taiwan/471/2008 71 8 49 13 71
JP 24 A/Brisbane/10/2007 71 7 40 8 71
24 A/Uruguay/716/2007 67 9 41 8 71
24 A/Brisbane/24/2008 58 9 41 8 75
24 A/Missouri/5/2008 46 8 26 4 63
24 A/Taiwan/471/2008 50 7 24 8 54
USA 24 A/Brisbane/10/2007 92 7 127 13 92
24 A/Uruguay/716/2007 92 11 135 25 92
24 A/Brisbane/24/2008 88 12 138 25 92
24 A/Missouri/5/2008 54 9 36 21 71
24 A/Taiwan/471/2008 54 8 24 13 54
9
A/Brisbane/10/2007-like VACCINESSUMMARY TABLEVIRUSES WITH
> 50% GMT REDUCTION
(ADULT)VIRUSES CBER CDC NIBSC AUS NIID TOTAL Total % REDUCED
A/BRISBANE/24/2008 0/3 0/3 1/3 4/4 0/4 5/17 28 (0-63)A/Missouri/5/2008 2/3 3/3 2/3 7/9 49 (10-73)A/Norway/2118/2008 1/3 1/3 29(0-51)A/Taiwan/471/2008 1/3 0/3 0/4 1/4 2/14 27(0-54)A/New York/09/2008 3/3 2/4 5/7 65 (42-79)A/Tennessee/04/2008 1/3 1/3 35 (8-60)A/Kanagawa/65/2008 4/4 4/4 79 (61-88)
25/57 40 (0-79)
12
A/Brisbane/10/2007-like VACCINESSUMMARY TABLEVIRUSES WITH
> 50% GMT REDUCTION
(ELDERLY)
13
VIRUSES CBER CDC NIBSC AUS NIID TOTAL Total % REDUCED
A/BRISBANE/24/2008 0/3 0/3 1/3 2/4 0/4 3/17 23 (0-70)A/Missouri/5/2008 2/3 2/3 2/3 6/9 55 (35-72)A/Norway/2118/2008 0/3 0/3 32(9-48)A/Taiwan/471/2008 2/3 0/3 0/4 1/4 3/14 29 (0-81)A/New York/09/2008 2/3 3/4 5/7 19 (43-83)A/Tennessee/04/2008 0/3 0/3 33 (14-33)A/Kanagawa/65/2008 4/4 4/4 81 (80-90)
25/57 34 (0-90)
A/Brisbane/10/2007-like VACCINESSUMMARY TABLEVIRUSES WITH
> 50% GMT REDUCTION
(Pediatric)
13
VIRUSES CBER CDC TOTAL Total % REDUCED
A/BRISBANE/24/2008 0/1 0/2 0/3 22 (0-25)A/Missouri/5/2008 1/1 2/2 3/3 73 (58-85)A/Taiwan/471/2008 1/1 1/1 52A/New York/09/2008 2/2 2/2 67 (63-70)A/Tennessee/04/2008 0/2 0/2 46 (45-46)
5/11 51 (0-85)
Antigens for Serology (B)VACCINE STRAIN-YamB/Florida/4/2006B/Brisbane/3/2008
REPRESENTATIVE CURRENT STRAINS
• B/Indiana/01/2008 • B/England/145/2008• B/Bangladesh/3333/2007• B/Cape Town/337/2008
• B/Fujian Gulou/1272/2008• B/Brisbane/33/2008• B/England/393/208• B/Tochigi/15/2008• B/Brisbane/60/2008• B/Perth/210/2008
14
HI ANTIBODY RESPONSES TO B ADULT POPULATION (Australia)
15
N Antigen % Rise
Pre-GMT
Post-GMT
Pre % > 40
Post % > 40
AUS 24 B/Brisbane/3/2008-Yam 90 19 166 40 95
24 B/Cape Town/337/2008-Yam 80 22 171 33 95
24 B/Indiana/1/2008-Yam 70 16 92 40 90
24 B/Brisbane/60/2008-Vic 30 17 40 35 55
24 B/Perth/210/2008-Vic 20 28 61 60 80
24 B/Fujian/Gulou/1272/2008-Vic 30 20 46 45 60
EU 24 B/Brisbane/3/2008-Yam 71 13 116 25 88
24 B/Cape Town/337/2008-Yam 83 17 190 33 100
24 B/Indiana/1/2008-Yam 79 13 120 25 100
24 B/Brisbane/60/2008-Vic 33 10 26 13 54
24 B/Perth/210/2008-Vic 42 12 39 29 67
24 B/Fujian/Gulou/1272/2008-Vic 25 15 31 25 88
HI ANTIBODY RESPONSES TO THE B COMPONENT ADULT POPULATION (Australia)
N Antigen % Rise
Pre-GMT
Post-GMT
Pre % > 40
Post % > 40
US 24 B/Brisbane/3/2008-Yam 42 62 214 67 100
24 B/Cape Town/337/2008-Yam 42 67 214 71 100
24 B/Indiana/1/2008-Yam 42 41 138 67 96
24 B/Brisbane/60/2008-Vic 38 25 52 46 75
24 B/Perth/210/2008-Vic 20 40 69 60 84
24 B/Fujian/Gulou/1272/2008-Vic 25 38 73 67 100
JP 24 B/Brisbane/3/2008-Yam 21 98 185 96 100
24 B/Cape Town/337/2008-Yam 21 69 116 88 96
24 B/Indiana/1/2008-Yam 21 39 73 71 92
24 B/Brisbane/60/2008-Vic 4 23 25 50 54
24 B/Perth/210/2008-Vic 4 29 27 63 67
24 B/Fujian/Gulou/1272/2008-Vic 8 29 34 67 71
HI ANTIBODY RESPONSES TO B Elderly POPULATION (Australia)
15
N Antigen% Rise
Pre-GMT
Post-GMT
Pre % > 40
Post % > 40
AUS 24 B/Brisbane/3/2008-Yam 45 27 102 60 100
24 B/Cape Town/337/2008-Yam 55 35 106 60 95
24 B/Indiana/1/2008-Yam 50 22 77 40 85
24 B/Brisbane/60/2008-Vic 15 11 22 20 40
24 B/Perth/210/2008-Vic 10 17 26 35 45
24 B/Fujian/Gulou/1272/2008-Vic 20 12 21 25 40
EU 24 B/Brisbane/3/2008-Yam 58 21 98 46 100
24 B/Cape Town/337/2008-Yam 44 22 109 67 133
24 B/Indiana/1/2008-Yam 63 13 69 33 92
24 B/Brisbane/60/2008-Vic 21 10 22 21 42
24 B/Perth/210/2008-Vic 21 14 29 21 54
24 B/Fujian/Gulou/1272/2008-Vic 17 12 22 46 100
HI ANTIBODY RESPONSES TO THE B COMPONENT Elderly POPULATION (Australia)
N Antigen % Rise
Pre-GMT
Post-GMT
Pre % > 40 Post % > 40
US 24 B/Brisbane/3/2008-Yam 38 39 113 67 100
24 B/Cape Town/337/2008-Yam 50 40 127 63 100
24 B/Indiana/1/2008-Yam 42 25 69 50 92
24 B/Brisbane/60/2008-Vic 17 26 38 54 54
24 B/Perth/210/2008-Vic 8 32 46 58 67
24 B/Fujian/Gulou/1272/2008-Vic 4 30 44 67 100
JP 24 B/Brisbane/3/2008-Yam 42 13 49 25 75
24 B/Cape Town/337/2008-Yam 42 13 41 29 67
24 B/Indiana/1/2008-Yam 42 10 36 8 50
24 B/Brisbane/60/2008-Vic 4 16 23 42 50
24 B/Perth/210/2008-Vic 13 19 28 46 54
24 B/Fujian/Gulou/1272/2008-Vic 8 20 28 46 50
B/Florida/4/2006 VACCINESSUMMARY TABLEVIRUSES WITH
> 50% GMT REDUCTION
(ADULT)
18
VIRUSES CBER CDC NIBSC AUS NIID TOTAL Total % REDUCED
B/England/145/2008-Yam 1/3 3/3 4/6 55 (25-77)
B/Indiana/01/2008 2/3 3/3 3/3 1/4 3/4 12/17 52 (0-79)
B/Bangladesh/3333/2007 2/4 2/4 44 (32-54)
B/Cape Town/337/2008 0/4 0/4 10 (0-39)18/31 46 (0-79)
B/Brisbane/33/2008-Vic 2/2 4/4 6/6 80 (76-85)
B/England/393/208 3/3 3/3 66 (53-81)
B/Fujian Gulou/1272/2008 1/3 3/3 1/3 4/4 4/4 13/17 59 (8-80)
B/Tochigi/15/2008 4/4 4/4 79 (71-90)
B/Brisbane/60/2008 3/3 2/3 4/4 9/10 69 (34-86)
B/Perth/210/2008 4/4 4/4 71 (63-86)39/44 67 (8-86)
B/Florida/4/2006 VACCINESSUMMARY TABLEVIRUSES WITH
> 50% GMT REDUCTION
(ELDERLY)
19
VIRUSES CBER CDC NIBSC AUS NIID TOTAL Total % REDUCED
B/England/145/2008 0/3 2/3 2/6 47 (25-76)
B/Indiana/01/2008 1/3 2/3 2/3 0/4 2/4 7/17 44 (26-65)
B/Bangladesh/3333/2007 1/4 1/4 39(23-50)
B/Cape Town/337/2008 0/4 0/4 4 (0-16)10/31 39 (0-79)
B/Brisbane/33/2008 2/2 3/4 5/6 72 (48-85)
B/England/393/208 2/3 2/3 48 (0-74)
B/Fujian Gulou/1272/2008 0/3 2/3 2/3 3/4 3/4 10/17 52 (0-81)
B/Tochigi/15/2008 2/4 2/4 54 (8-87)
B/Brisbane/60/2008 3/3 1/3 4/4 8/10 55 (0-78)
B/Perth/210/2008 3/4 3/4 62 (43-75)30/44 56 (0-85)
B/Florida/4/2006 VACCINESSUMMARY TABLEVIRUSES WITH
> 50% GMT REDUCTION
(Paediatric)
19
VIRUSES CBER CDCNIIDTOTAL Total % REDUCED
B/England/145/2008 1/1 1/1 50
B/Indiana/01/2008 0/1 0/1 0/2 44 (40-47)
1/3 46 (40-47)
B/Fujian Gulou/1272/2008 0/1 0/1 0/2 19 (6-32)
B/Brisbane/60/2008 1/1 0/1 1/2 52 (45-59)
1/4 35 (6-59)
Serologic ConclusionsStudies with human sera collected after immunization
with current vaccines show that:• H1N1
– Representative recent viruses were modestly inhibited by HA antibodies to current vaccine strains (A/Brisbane/59/2007-like virus).
• H3N2– Representative recent viruses were well inhibited by HA
antibodies to current vaccine strain (A/Brisbane/10/2007-like virus).
• B– B/VICTORIA/2/87-lineage
• Representative recent viruses were not well inhibited by HA antibodies to current vaccine strain (B/Florida/4/2006-like virus).
– B/YAMAGATA/16/88-lineage• Representative recent viruses were well inhibited by HA antibodies to the current vaccine strain.
20
