Influenza Vaccine Responses

Zhiping Ye, M.D., Ph.D.Division of Viral Products

Prepared for Vaccines and Related Biological

Products Advisory Committee17 February 2006

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2005-2006 Vaccine Responses to Recent Influenza isolates

• Panels of sera obtained from 2005-2006 influenza vaccinees were tested for their ability to inhibit heamagglutination of current influenza isolates

• Post-vaccination antibody titer of current virus isolates compared to vaccine strain of virus (bold)

• Lower titers (italic) indicate poor antibody inhibition of tested virus isolates

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1. AUSTRALIA IAN BARR, PH.D. ADULTS A/NEW CALEDONIA/20/99 (H1N1) WHO, AUSTRALIA ELDERLY A/WELLINGTON/01/04 (H3N2)

B/JIANSU/10/03 2. EUROPE JOHN WOOD, PH.D. ADULTS A/NEW CALEDONIA/20/99 (H1N1) NIBSC, ENGLAND ELDERLY A/NEW YORK/55/04 (H3N2)

B/JIANGSU/10/03 3. JAPAN TAKATO ODIGARI, PH.D. ADULTS A/NEW CALEDONIA/20/99 (H1N1) NIID, JAPAN ELDERLY A/NEW YORK/55/04 (H3N2)

B/SHANGHAI/361/02 4. STEFAN GRAVENSTEIN, M.D. ADULTS A/NEW CALEDONIA/20/99 (H1N1) EASTERN VIRGINIA ELDERLY A/NEW YORK/55/04 (H3N2) MEDICAL SCHOOL, PEDIATRIC B/JIANGSU/10/03 USA

Serum Panels for Serologies

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ANTIGENS FOR SEROLOGIES (H3N2)

VACCINE STRAINA/New York/55/04 X-157

REPRESENTATIVE CURRENT STRAINS• A/Wisconsin/76/05 • A/Hiroshima/52/05 • A/Anhui/1239/05 • A/Brazil/1742/05 • A/North Carolina/13/05 • A/Sydney/545/05 • A/Lyon/21/06• A/Norway/28/06• A/Gunama/16/05• A/Nagasaki/50/05

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HI ANTIBODY RESPONSES TO THE H3N2 COMPONENT2005-2006 INFLUENZA VACCINEPEDIATRIC POPULATION

STUDY N ANTIGEN % RISE PRE POST PRE POST

CDC 24 A/NEW YORK/55/04 X-157 89 11 84 21 75A/BRAZIL/1742/05 79 10 73 21 75

Age (Months) A/WISCONSIN/67/05 50 10 34 21 43Range 8-38 A/HIROSHIMA/52/05 32 9 24 21 32Mean 21 A/ANHUI/1239/05 57 9 33 21 39

A/NORTH CAROLINA/13/05 36 8 19 14 21

CBER 30 A/NEW YORK/55/04 X-157 71 10 222 18 82A/WISCONSIN/67/05 54 12 48 21 46A/HIROSHIMA/52/05 71 12 66 21 54A/ANHUI/1239/05 82 12 12 25 68

UK 19 A/NEW YORK/55/04 X-157 74 22 361 37 100A/ANHUI/1239/05 74 18 225 32 95A/WISCONSIN/67/05 68 21 235 32 95A/LYON/21/06 68 26 134 37 10A/NORWAY/28/06 74 17 127 32 95A/HIROSHIMA/52/05 79 16 157 26 90

GMT % HI > 40

SEROLOGIES POST 2 DOSES VACCINE 5

HI ANTIBODY RESPONSES TO THE H3N2 COMPONENT2005-2006 INFLUENZA VACCINEADULT POPULATION ( CBER )

STUDY N ANTIGEN % RISE PRE POST PRE POST

EU 24 A/NEW YORK/55/04 X-157 100 <8 181 13 92A/ANHUI/1239/05 100 <8 271 13 96A/HIROSHIMA/52/05 96 <8 140 8 92A/WISCONSIN/67/05 88 <8 76 0 88

JAPAN 24 A/NEW YORK/55/04 X-157 60 <8 40 7 40A/ANHUI/1239/05 36 <8 21 14 36A/HIROSHIMA/52/05 50 <8 23 10 40A/WISCONSIN/67/05 30 <8 11 7 23

USA 24 A/NEW YORK/55/04 X-157 92 10 383 29 96A/ANHUI/1239/05 88 16 362 48 91A/HIROSHIMA/52/05 96 12 192 25 96A/WISCONSIN/67/05 88 <8 117 17 79

GMT % HI > 40

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A/NEW YORK/55/2004 VACCINESSUMMARY TABLE (ADULT)

VIRUSES WITH > 50% GMT REDUCTION

VIRUSES CBER CDC NIBSC AUS NIID TOTAL % REDUCED

A/WISCONSIN/67/2005 3/3 0/3 0/3 0/3 3/12 43 (21-73)

A/HIROSHIMA/52/2004 0/3 0/3 0/3 0/3 1/3 1/15 24 (0-50)

A/N. CAROLINA/13/2005 2/3 2/3 65 (43-78)

A/LYON/21/2006 3/3 3/3 82 (65-90)

A/GUNMA/16/2005 3/3 3/3 73 (65-84)

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ANTIGENS FOR SEROLOGIES (B)

VACCINE STRAINB/JIANGSU/10/2003*

REPRESENTATIVE CURRENT STRAINSB/FLORIDA/7/2004* B/KITAKYUSYU/5/2005*B/GANSU/9/2005* B/PHILIPPINES/1401/2005*B/MADAGASCAR/1509/2005* B/EGYPT/144/2005*

B/MALAYSIA/2506/2004+ B/OHIO/1/2005+B/GUANGONG/321/2005+B/ENGLAND/458/2005+B/SINGAPORE/21/2005+

* B/YAMAGATA LINEAGE+ B/VICTORIA LINEAGE

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HI ANTIBODY RESPONSES TO THE B COMPONENT2005-2006 INFLUENZA VACCINE

PEDIATRIC POPULATION STUDY N ANTIGEN % RISE PRE POST PRE POST

CDC 24 B/JIANGSU/10/2003* 68 6 28 7 54B/FLORIDA/07/2004* 46 6 22 7 36B/GANSU/9/2005* 39 6 14 4 29B/MALAYSIA/2506/2004+ 0 5 5 0 0B/OHIO/1/2005+ 0 5 5 0 0B/GUANGDONG/321/2005+ 0 5 5 0 0

CBER 30 B/JIANGSU/10/2003* 57 <8 20 4 32B/FLORIDA/07/2004* 11 <8 5 0 7B/MALAYSIA/2506/2004+ 0 <8 4 0 0B/OHIO/1/2005 + 0 <8 4 0 0

UK 19 B/JIANGSU/10/2003* 84 7 101 5 84B/FLORIDA/07/2004* 16 6 13 5 16B/ENGLAND/458/2005* 11 5 8 0 10B/MADAGASCAR/1509/2005* 58 6 40 5 58B/MALAYSIA/2506/2004+ 5 5 9 0 5B/OHIO/1/2005 + 5 5 8 0 5

GMT % HI > 40

* =YAMAGATA LINEAGE + = VICTORIA LINEAGESEROLOGIES POST 2 DOSES VACCINE

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HI ANTIBODY RESPONSES TO THE B COMPONENT2005-2006 INFLUENZA VACCINE

ADULT POPULATION (CDC)

STUDY N ANTIGEN % RISE PRE POST PRE POST

USA 24 B/JIANGSU/10/2003* 71 14 98 25 92B/FLORIDA/07/2004* 58 38 151 67 100B/GANSU/9/2005* 63 21 87 46 96B/MALAYSIA/2506/2004+ 17 14 83 17 38B/OHIO/1/2005 X B/LEE+ 21 14 24 17 42B/GUANGDONG/321/2005+ 22 12 22 17 33

EU 24 B/JIANGSU/10/2003* 88 7 76 0 79B/FLORIDA/07/2004* 74 21 170 43 96B/GANSU/9/2005* 65 12 80 22 88B/MALAYSIA/2506/2004+ 22 6 11 0 13B/OHIO/1/2005 X B/LEE+ 26 6 11 0 8B/GUANGDONG/321/2005+ 22 6 9 0 8

GMT % HI > 40

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B/JANGSU/10/2003-LIKE VACCINESSUMMARY TABLE

VIRUSES WITH > 50% GMT REDUCTION (ADULT)

VIRUSES CBER CDC NIBSC AUS NIID TOTAL % REDUCED

B/MALAYSIA/2506/2005+ 2/3 2/3 3/4 7/10 63 (0-91)

B/OHIO/1/2005+ 2/3 2/3 4/4 3/4 3/4 14/18 67 (0-95)

B/GUANGDONG/321/2005+ 2/3 2/3 55 (0-88)

B/FLORIDA/7/2004 * 2/3 0/3 3/4 3/4 8/14 48 (0-80)

B/MADAGASCAR/1509/2005 * 0/4 0/4 9 (0-34)

B/GANSU/9/2005 * 0/3 0/3 4 (0-11)

* = YAMAGATA LINEAGE + =VICTORIA LINEAGE

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Influenza Vaccine ResponsesSummary

Studies with sera collected after immunization with current vaccines show that:

• H1– Representative recent viruses well inhibited (data not

shown)• H3

– A/WISCONSIN/67/2005 (H3N2)-like viruses less well inhibited compared to the vaccine strain

• B – B/YAMAGATA/16/88-lineage

• Representative recent viruses generally well inhibited compared to the vaccine strain

– B/VICTORIA/2/87-lineage• Representative B/Malaysia/2506/2004-like viruses poorly

inhibited compared to the vaccine strain

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