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 Committee22 February 2010

Inactivated Vaccine Serology Studies

Sera from vaccine recipients was analyzed for the presence of antibodies to the HA of recent virus isolates

– Hemagglutination inhibition (HI) titers for recent isolates compared to HI titer of the vaccine virus

Pandemic H1N1 isolates analyzed using over13 panels of sera from adults, elderly, and pediatric populations receiving pandemic H1N1 inactivated vaccines

– Included representative pandemic H1N1 isolates as well as low reactors (determined using post-infection ferret antiserum)

Recent A/H3N2 and B isolates analyzed using 9 panels of sera from adults, elderly and pediatric populations receiving seasonal trivalent inactivated vaccine (2009-2010)

– Due to predominance of pandemic H1N1 isolates, antibody response to seasonal H1N1 not analyzed

Serum Panels Used for Serology

(Seasonal)

AUSTRALIA, IAN BARR, PH.D. ADULTS A/Brisbane/59/2007 IVR-148 (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/Brisbane/60/2008

JAPAN, TAKATO ODIGARI, PH.D. ADULTS A/Brisbane/59/2007 IVR-148 (H1N1) )

NIID, JAPAN ELDERLY A/Uruguay/716/2007 NYMC X175C(H3N2)

B/Brisbane/60/2008

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/Brisbane/60/2008

Serum Panels Used for SerologyPandemic A(H1N1) 2009

AUSTRALIA, IAN BARR, PH.D. ADULTS(18-64 Yr.) A/California/07/2009 (X179A)

WHO, AUSTRALIA CHILDREN (6 mon-17Yr)

CHINA, YUELONG SHU PH.D. ADULTS (18-59) A/California/07/2009 (X179A)

BEIJING, CHINA ADOLESCENCE (10-17 Yr)

CHILDREN (3-9 Yr)

EUROPE, JOHN WOOD, PH.D. ADULTS (18-59) A/California/07/2009 (X179A)*

NIBSC, ENGLAND ADOLESCENCE (10-17 Yr)

CHILDREN (3-9Yr)

USA, Linda Lambert, Ph.D. ADULTS (18-64Yr) A/California/07/2009 (X179A)

NIH, USA ELDERLY (> 65 Yr)

CHILDREN (6 mon-17Yr)

*= Adjuvanted or non-adjuvanted

Antigens for Serology (pandemic H1N1)

VACCINE STRAIN

A/CALIFORNIA/7/2009 NYMC X-179A

RECENT VIRUS ISOLATES TESTED

• A/England/195/2009• A/Guam/2125/2009• A/Kobe/92297/2009• A/Lviv/N6/2009• A/IRAQ/8529/2009• A/Ontario/RV3226/2009• A/South Carolina/18/2009• A/Utah/20/2009

• A/Brisbane/59/2007 (IVR-148): Seasonal H1N1 as a control

Antigens for serology pandemic A(H1N1) 2009

(by Derek Smith, U of Cambridge)

A/California/07/2009NYMC X-179A

Antigens for serology pandemic A(H1N1) 2009

A/England/195/2009

A/Guam/2125/2009

A/Lviv/N6/2009

A/Ontario/RV3226/2009

A/South Carolina/18/2009

A/Kobe/92297/2009

A/Iraq/8529/2009

A/Utah/20/2009

EXAMPLE OF HI ANTIBODY RESPONSES TO THE PANDEMIC A(H1N1) COMPONENT

CDC, ADULT POPULATIONTRIAL NO.

OFSERA

VIRUS STRAIN GMT PRE POST

UK

16 A/CALIFORNIA/7/2009 X-179A*A/ENGLAND/195/2009A/IRAQ/8529/2009A/SOUTH CAROLINA/18/2009A/ONTARIO/RV3226/2009A/BRISBANE/59/2007 (seasonal)

556558

2932581531299113

US 25 A/CALIFORNIA/7/2009 X-179A*A/ENGLAND/195/2009A/IRAQ/8529/2009A/SOUTH CAROLINA/18/2009A/ONTARIO/RV3226/2009A/BRISBANE/59/2007 (seasonal)

75756

19

55758947236839939

AU 16 A/CALIFORNIA/7/2009 X-179A*A/ENGLAND/195/2009A/IRAQ/8529/2009A/SOUTH CAROLINA/18/2009A/ONTARIO/RV3226/2009A/BRISBANE/59/2007 (seasonal)

87665

17

1117844323425


CDC, ELDERLY POPULATION

TRIAL NO.OFSERA


US 25 A/CALIFORNIA/7/2009 X-179A*A/ENGLAND/195/2009A/IRAQ/8529/2009A/SOUTH CAROLINA/18/2009A/ONTARIO/RV3226/2009A/BRISBANE/59/2007 (seasonal)

171519131217

26430321114315124


CDC, CHILDREN POPULATIONTRIAL NO.

OFSERA


UK3-9Y


65655

30

94583023619916040

UK 10-17Y


75756

19

538381129848759

US 6M-17Y


87665

17

22324385614214

SUMMARY OF HI ANTIBODY RESPONSES TO THE PANDEMIC A(H1N1) 2009 COMPONENT

0

25

50

75

100

125

150

X-179A A/ENGLAND A/IRAQ A/ONTARIO A/SC SEASONAL

% p

ost

GM

T

ADULT

ELDERLY

CHILDREN

Antigens for Serology (H3N2)

VACCINE STRAIN

A/Brisbane/10/2007A/Uruguay/716/2007

RECENT VIRUS ISOLATES TESTEDA/Wisconsin/15/2009 X183 A/Perth/16/2009 A/Hong Kong/26560/2009 A/Shizuoka/736/2009A/Philippines/2191/2009 A/Victora/208/2009 A/Hunan-Beihu/1313/09

EXAMPLE OF HI ANTIBODY RESPONSES TO H3N2 COMPONENT

CDC, ADULT POPULATION

TRIAL TESTSITE

NO.OFSERA


UK 24 A/URUGUAY/716/07 X-175C *A/VICTORIA/208/2009A/WISCONSIN/15/2009 X-183A/HONGKONG/26560/2009

131578

23315180

110

US

24 A/URUGUAY/716/07 X-175C *A/VICTORIA/208/2009A/WISCONSIN/15/2009 X-183A/HONGKONG/26560/2009

13157

21

277827382

EXAMPLE OF HI ANTIBODY RESPONSES TO THE H3N2 COMPONENT

CBER, ELDERLY POPULATION

TRIAL TESTSITE

NO.OFSERA


UK 24 A/URUGUAY/716/07 X-175C *A/VICTORIA/208/2009A/WISCONSIN/15/2009 X-183A/HONGKONG/26560/2009A/PHILIPPINES/2191/2009

2221969

190138872549

US 24 A/URUGUAY/716/07 X-175C *A/VICTORIA/208/2009A/WISCONSIN/15/2009 X-183A/HONGKONG/26560/2009A/PHILIPPINES/2191/2009

1213766

10452521223

EXAMPLE OF HI ANTIBODY RESPONSES TO THE H3N2 COMPONENT

CBER, CHILDREN POPULATION

TRIAL NO. OFSERA


PEDIATRIC 22 A/URUGUAY/716/07 X-175C *A/VICTORIA/208/2009A/WISCONSIN/15/2009 X-183A/HONGKONG/26560/2009A/PHILIPPINES/2191/2009

87666

21985883555

SUMMARY OF HI ANTIBODY RESPONSES TO H3N2 COMPONENT

0

10

20

30

40

50

60

70

80

90

100

110

* = In children panel

% P

os

t G

MT

ADULT

ELDERLY

CHILDREN

Antigens for Serology (B)

VACCINE STRAIN-VicB/Brisbane/60/2008

RECENT VIRUS ISOLATES TESTED• B/Bangladesh/5945/2009 • B/Hong Kong/230/2009 • B/Laos/1232/2009 • B/Philippines/6363/2009

Control viruses

• B/Florida/4/2006-Yam• B/Brisbane/3/2007-Yam• B/Bangladesh/3333/2007-Yam

EXAMPLE OF HI ANTIBODY RESPONSES TO THE B COMPONENT

CBER, ADULT POPULATION

TRIAL NO.OFSERA


UK 24 B/BRISBANE/60/2008-VIC*B/FLORIDA/4/2006-YAMB/HONG KONG/230/2009-VICB/BANGLADESH/5945/2009-VIC

8156

13

80486052

US 24 B/BRISBANE/60/2008-VIC*B/FLORIDA/4/2006-YAMB/HONG KONG/230/2009-VICB/BANGLADESH/5945/2009-VIC

5566

41174433

EXAMPLE OF HI ANTIBODY RESPONSES TO THE B COMPONENT

CBER, ELDERLY POPULATION

TRIAL VIRUS STRAIN GMT PRE POST

UK B/BRISBANE/60/2008-VIC*B/FLORIDA/4/2006-YAMB/HONG KONG/230/2009-VICB/BANGLADESH/5945/2009-VIC

12141114

53314642

US

B/BRISBANE/60/2008-VIC*B/FLORIDA/4/2006-YAMB/HONG KONG/230/2009-VICB/BANGLADESH/5945/2009-VIC

6597

159

2617

HI ANTIBODY RESPONSES TO THE B COMPONENT CDC, CHILDREN POPULATION

TRIAL VIRUS STRAIN GMT PRE POST

US B/BRISBANE/60/2008-VIC* B/BANGLADESH/3333/2007-YAM B/BANGLADESH/5945/2009-VIC B/HONG KONG/230/2009-VIC

77 76

60225735

SUMMARY OF HI ANTIBODY RESPONSES TO B COMPONENT

Victoria-lineage

0102030405060708090

100110

*= In children panel

% P

ost

GM

TADULT

ELDERLY

CHILDREN

SUMMARY OF HI ANTIBODY RESPONSES TO B COMPONENT

Yamagata-lineage

0

10

20

30

40

50

60

70

80

90

100

110

* = In children panel

% P

os

t G

MT

ADULT

ELDERLY

CHILDREN

Conclusions from Human Serology Studies

H1N1– Representative recent pandemic A(H1N1) virus isolates well

covered by vaccine containing A/California/07/2009 H3N2

– Many recent virus isolates showed significant reductions in GMT when tested with sera from recipients of vaccine containing A/Uruguay/716/2007

B– B/VICTORIA/2/87-lineage

• Recent virus isolates were well covered by current vaccine – B/YAMAGATA/16/88-lineage

• Recent virus isolates were less well covered by current vaccine

influenza vaccine responses

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