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 2014

Inactivated Vaccine Serology Studies

Purpose: Evaluation of anti-HA antibody titers to recent viruses as compared to those of the recommended vaccine viruses in children, adults and older adults who had received trivalent or quadrivalent inactivated vaccine (2013-2014 formulation).

Serum samples: Five panels of sera from adults, 5 panels from older adults and 2 panels from pediatric populations were analyzed from trivalent vaccine trials. One panel of sera each from pediatric, adults and older adult was analyzed from a quadrivalent vaccine trial. Sera were collected prior to and 21-28 days post-vaccination. Most of the panels were pre-screened to avoid sera with low antibody titers.

Methods: Hemagglutination inhibition (HI) assays were used to determine HI titers to recent viruses compared to HI titers of the corresponding vaccine virus. A subset of sera was tested by micro-neutralization assay. The serum panels were distributed to and tested in 6 laboratories. 2

Serum panels used for studies: seasonal trivalent

vaccineAUSTRALIA ADULTS OLDER ADULTS

A/California/7/2009 (H1N1pdm09) (NYMC X-179A) A/Victoria/361/2011 (H3N2) (IVR-165)

B/Hubei-Wujiagang/158/2009 (NYMC BX-39)

CHINA CHILDREN (4Yr)ADULTS

OLDER ADULTS

A/Christchurch/16/2010 (H1N1pdm09) (NIB-74xp) A/Texas/50/2012 (H3N2) (NYMC X-223A) B/Massachusetts/2/2012 (NYMC BX-51B)

EUROPE ADULTS OLDER ADULTS

A/Christchurch/16/2010 (H1N1pdm09) (NIB-74xp) A/Texas/50/2012 (H3N2) (NYMC X-223)

B/Massachusetts/2/2012

EUROPE ADULTS OLDER ADULTS

A/Brisbane/10/2010 (H1N1pdm09) A/Texas/50/2012 (H3N2) (NYMC X-223A)

B/Massachusetts/2/2012

JAPAN ADULTSOLDER ADULTS

A/California/7/2009 (H1N1pdm09) (NYMC X-179A) A/Texas/50/2012 (H3N2) (NYMC X-223)

B/Massachusetts/2/2012 (NYMC BX-51B)

USA(CDC contract)

CHILDREN (1.7Yr) A/California/7/2009 (H1N1pdm09) (NYMC X-179A) A/Texas/50/2012 (H3N2) (NYMC X-223A)

B/Massachusetts/2/2012

4

Serum panels used for studies: seasonal

quadrivalent vaccineUSA

(Donated by a US mfr).

CHILDREN (3.5Yr)ADULTS

OLDER ADULTS

A/California/7/2009 (H1N1pdm09) (NYMC X-179A) A/Texas/50/2012 (H3N2) (NYMC X-223A)

B/Massachusetts/2/2012B/Brisbane/60/2008

5

A(H1N1)pdm09 Serology

Antigens for serology: A(H1N1)pdm09

REFERENCE VIRUS

A/California/7/2009

REPRESENTATIVE CURRENT VIRUSES

A/New Hampshire/4/2013 Egg

A/Mississippi/10/2013 Egg

A/Massachusetts/15/2013 Egg

A/Sichuan-Wuhou/2259/2013 Egg

A/Lisbon/137/2013 Cell

A/Massachusetts/15/2013 Cell

A/Pennsylvania/07/2013 Cell

A/Brisbane/205/2013 Cell

A/Singapore/GP1796/2013 Cell

A/Wakayama/153/2013 Cell

HI ANTIBODY RESPONSES TO THE A(H1N1)pdm09 COMPONENT (% GMT)

rela

tive

GM

Tre

lativ

e G

MT

Egg-ref Egg-ref virusvirus Egg or cell isolatesEgg or cell isolates

7

A(H1N1)pdm09-summary

Vaccines containing A/California/7/2009 antigens elicited anti-HA antibodies of similar geometric mean HI titers to the vaccine virus and the majority of representative A(H1N1)pdm09 viruses

8

9

A(H3N2) Serology

Antigens for serology:A(H3N2)

REFERENCE VIRUS

A/Texas/50/2012 egg or cell

REPRESENTATIVE CURRENT VIRUSES

A/New York/39/2012 egg

A/New York/39/2012 cell

A/Utah/07/2013 egg

A/Utah/07/2013 cell

A/Almaty/2958/2013 Egg

A/Massachusetts/11/2013 Egg

A/Victoria/506/2013 Egg

A/Jiangxi-Xunyang/1790/2013 Cell

A/Louisiana/09/2013 Cell

A/Tokyo/31512/2013 Cell

=Egg and cell pair

HI ANTIBODY RESPONSES TO THE A(H3N2) COMPONENT:using A/Texas/50/2012 egg-grown virus as reference

rela

tive

GM

Tre

lativ

e G

MT Eg

g-gr

own

ref.

Egg-isolatesEgg-isolates

Cell isolatesCell isolates

11

HI ANTIBODY RESPONSES TO THE A(H3N2) COMPONENT:using A/Texas/50/2012 cell-grown virus as reference

Egg-isolates

rela

tive

GM

T

12

Cel

l-gro

wn

Cel

l-gro

wn

ref

ref.

Cell isolatesCell isolates

A(H3N2)-summary

Vaccines containing A/Texas/50/2012 antigens induced anti-HA antibodies of similar geometric mean HI titers (GMT) to recent egg-propagated A(H3N2) viruses as to the vaccine virus. Reduced GMTs were observed for some recent cell-propagated viruses when compared to titers to the egg-propagated vaccine viruses.

13

14

Influenza B Serology

Antigens for serology:influenza B

REFERENCE VIRUSES

B/Massachusetts/2/2012 egg and cell (Yam)

B/Brisbane/60/2008 egg (Vic, quadrivalent vaccine only)

REPRESENTATIVE CURRENT VIRUSES

Yamagata lineage

B/Arizona/8/2013 Cell

B/Chongqing-Yuzhong/11616/2013 Egg

B/Lithuania/6935/2013 Cell

B/Shandong-Mudan/1374/2013 Cell

B/Guatemala/8/2013 Cell

B/Hong Kong/315/2013 Cell

B/Phuket/3073/2013 Egg

B/Townsville/15/2013 Cell

B/Osaka/18/2013 Cell

Victoria lineage

B/Brisbane/60/2008 Egg

B/Texas/2/2013 Egg

B/Texas/2/2013 Cell

B/Ghana/1118/2013 Cell

B/Jiangsu-Tianning/1796/2013 egg

rela

tive

GM

T

16

Yam-like isolatesYam-like isolates

Vic-like isolatesVic-like isolates

All

Yam

-like

isol

ates

All

Yam

-like

isol

ates

All

Vic-

like

isol

ates

All

Vic-

like

isol

ates

HI ANTIBODY RESPONSES TO THE B-Yam COMPONENT (% GMT)

rela

tive

GM

T

17

HI ANTIBODY RESPONSES TO THE B-Vic COMPONENT of QUADRIVALENT

VACCINHE (% GMT)

B-summary

Vaccines containing B/Massachusetts/2/2012 )Yam( antigen elicited anti-HA antibodies of similar geometric mean titers to the vaccine virus and the majority of representative recent Yam-lineage viruses, and as expected,elicited anti-HA antibodies of lower titers to representative recent Vic-lineage viruses. Vaccines containing B/Massachusetts/2/2012 and B/Brisbane/60/2008 )Vic( antigens elicited anti-HA antibodies of similar geometric mean titres to the vaccine viruses and the majority of representative recent Yam- and the Vic-lineage viruses.

18

Summary H1N1pdm09

– Vaccines containing A/California/7/2009-like antigens stimulated anti-HA antibodies of geometric mean titers to representative recent A(H1N1)pdm09 viruses that were not significantly reduced as compared to titers against A/California/7/2009-like reference viruses

H3N2– Vaccines containing A/Texas/50/2012 antigens induced anti-HA antibodies of similar

geometric mean HI titers (GMT) to the recent egg-propagated A(H3N2) viruses, but lower GMTs to some recent cell-propagated viruses, when compared to the egg-propagated vaccine viruses.

B– Vaccines containing B/Massachusetts/2/2012 (Yam) antigen elicited anti-HA antibodies of

similar geometric mean titers to the vaccine virus and the majority of representative recent Yam-lineage viruses, and elicited the antibodies of low titers to the representative recent Vic-lineage viruses.

– Vaccines containing B/Massachusetts/2/2012 and B/Brisbane/60/2008 (Vic) antigens elicited anti-HA antibodies of similar geometric mean titers to the vaccine viruses and the majority of representative recent Yam- and the Vic-lineage viruses.

19