# Presentation: 340052

## Influenza Vaccine Responses 

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

**Prepared for **
**Vaccines and Related Biological **
**Products Advisory Committee**
**21 February 2008**

## Serum panels used for serology 

**AUSTRALIA, IAN BARR, PH.D. ****	****	****ADULTS ****	****        ****A/NEW CALEDONIA/20/99 IVR-116 (H1N1) **
**WHO, AUSTRALIA ****	****	****	****ELDERLY ****	****        A/WISCONSIN/67/2005 X161B (H3N2)**
**	****	****	****	****	****        ****B/MALAYSIA/2506/2005 **
**EUROPE, JOHN WOOD, PH.D. ****	****	****ADULTS ****	****        A/SOLOMON ISLANDS/03/2006 IVR-145 (H1N1) **
**NIBSC, ENGLAND ****	****	****	****ELDERLY ****	****        A/WISCONSIN/67/2005 X161B (H3N2) **
**	****	****	****	****	****       ****B/MALAYSIA/2506/2005 **
**JAPAN, TAKATO ODAGARI, PH.D. ****	****ADULTS ****	****       A/SOLOMON ISLANDS/03/2006 IVR-145 (H1N1) **
** ****NIID, JAPAN ****	****	****	****ELDERLY ****	****       ****A/HIROSHIMA/52/2006 IVR-142 (H3N2)**** ****	**
**	****	****	****	****	****       ****B/MALAYSIA/2506/2005 **
**USA, STEFAN GRAVENSTEIN, M.D. ****	****ADULTS ****	****       A/SOLOMON ISLANDS/03/2006 IVR-145 (H1N1) **
**EASTERN VIRGINIA ****	****	****	****ELDERLY ****	****       A/WISCONSIN/67/2005 X161B (H3N2) **
**MEDICAL SCHOOL****	****	****	****PAEDIATRIC     B/MALAYSIA/2506/2005 ****	****	****	****	****	****	****	**
**	****	****	****	****	****	**

**1**

## Antigens for serology (H1N1)

_**VACCINE STRAIN**_
**A/Solomon Islands/03/2006 IVR-145**
_**REPRESENTATIVE CURRENT STRAINS**_
**A/Brisbane/59/2007    ****	**
**A/Egypt/10/2007         ****	**
**A/Hiroshima/93/2007 ****	**
***A/Netherlands/345/2007***** ****	**
***A/Norway/1747/2007***** ****	**
***A/Paris/0641/2007***** ****	****	**
**A/South Dakota/6/2007 ****	****	**** **
**A/Cambodia/0371/2007 ****	**
**A/Brisbane/3/2006****	****	**

**2**

## HI ANTIBODY RESPONSES TO THE H1N1  ADULT POPULATION (CBER)

**3**

|  | N | Antigen | % Rise | Pre-
vacc
GMT | Post-
vacc
GMT | Pre-
vacc %  
HI>40 | Post- vacc %  
HI>40 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| EU | 24 | A/Solomon Island/03/2006 | 96 | 12 | 724 | 25 | 96 |
|  | 24 | A/Florida/3/2006 | 83 | 10 | 161 | 21 | 83 |
|  | 24 | A/Brisbane/59/2007 | 54 | 4 | 21 | 4 | 42 |
|  | 24 | A/Cambodia/0371/2007 | 42 | 4 | 13 | 0 | 38 |
|  | 24 | A/South Dakota/06/2007 | 75 | 4 | 44 | 0 | 63 |
| Japan | 30 | A/Solomon Island/03/2006 | 50 | 28 | 109 | 46 | 75 |
|  | 30 | A/Florida/3/2006 | 21 | 25 | 51 | 50 | 67 |
|  | 30 | A/Brisbane/59/2007 | 21 | 7 | 10 | 13 | 29 |
|  | 30 | A/Cambodia/0371/2007 | 17 | 6 | 8 | 13 | 21 |
|  | 30 | A/South Dakota/06/2007 | 33 | 11 | 24 | 29 | 58 |
| USA | 24 | A/Solomon Island/03/2006 | 52 | 92 | 1248 | 81 | 100 |
|  | 24 | A/Florida/3/2006 | 33 | 109 | 434 | 90 | 95 |
|  | 24 | A/Brisbane/59/2007 | 62 | 3 | 124 | 29 | 86 |
|  | 24 | A/Cambodia/0371/2007 | 52 | 9 | 56 | 19 | 76 |
|  | 24 | A/South Dakota/06/2007 | 52 | 12 | 102 | 33 | 71 |

## HI ANTIBODY RESPONSES TO THE H1N1  ELDERLY   POPULATION (CBER)

**4**

|  | N | Antigen | % Rise | Pre-
vacc
GMT | Post-
vacc
GMT | Pre-
vacc %  
HI>40 | Post- vacc %  
HI>40 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| EU | 24 | A/Solomon Island/03/2006 | 92 | 7 | 161 | 8 | 96 |
|  | 24 | A/Florida/3/2006 | 83 | 8 | 91 | 17 | 88 |
|  | 24 | A/Brisbane/59/2007 | 50 | 5 | 33 | 8 | 50 |
|  | 24 | A/Cambodia/0371/2007 | 58 | 5 | 38 | 4 | 58 |
|  | 24 | A/South Dakota/06/2007 | 67 | 6 | 40 | 8 | 58 |
| Japan | 30 | A/Solomon Island/03/2006 | 71 | 6 | 54 | 8 | 63 |
|  | 30 | A/Florida/3/2006 | 46 | 5 | 25 | 4 | 33 |
|  | 30 | A/Brisbane/59/2007 | 29 | 5 | 11 | 8 | 33 |
|  | 30 | A/Cambodia/0371/2007 | 29 | 5 | 12 | 4 | 29 |
|  | 30 | A/South Dakota/06/2007 | 42 | 6 | 17 | 8 | 33 |
| USA | 24 | A/Solomon Island/03/2006 | 92 | 14 | 279 | 38 | 100 |
|  | 24 | A/Florida/3/2006 | 71 | 18 | 64 | 50 | 79 |
|  | 24 | A/Brisbane/59/2007 | 54 | 5 | 26 | 0 | 50 |
|  | 24 | A/Cambodia/0371/2007 | 50 | 4 | 28 | 0 | 54 |
|  | 24 | A/South Dakota/06/2007 | 67 | 6 | 38 | 8 | 58 |

## HI ANTIBODY RESPONSES TO THE H1N1  PEDIATRIC   POPULATION (CDC-CBER)

**5**

|  | N | Antigen | % Rise | Pre-
vacc
GMT | Post-
vacc
GMT | Pre-
vacc %  
HI>40 | Post- vacc %  
HI>40 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| US* | 15 | A/Solomon Island/03/2006 | 10 | 5 | 202 | 8 | 96 |
|  | 15 | A/Brisbane/59/2007 | 53 | 5 | 26 | 8 | 50 |
|  | 15 | A/Cambodia/0371/2007 | 47 | 5 | 15 | 4 | 58 |
|  | 15 | A/South Dakota/06/2007 | 67 | 5 | 23 | 8 | 58 |
| US | 29 | A/Solomon Island/03/2006 | 96 | 6 | 129 | 8 | 63 |
|  | 29 | A/Brisbane/59/2007 | 69 | 6 | 33 | 4 | 33 |
|  | 29 | A/Cambodia/0371/2007 | 52 | 6 | 25 | 4 | 29 |
|  | 29 | A/South Dakota/06/2007 | 52 | 6 | 29 | 8 | 33 |
| US | 32 | A/Solomon Island/03/2006 | 100 | 5 | 223 | 38 | 100 |
|  | 32 | A/Florida/3/2006 | 76 | 6 | 64 | 50 | 79 |
|  | 32 | A/Brisbane/59/2007 | 76 | 4 | 57 | 0 | 50 |
|  | 32 | A/Cambodia/0371/2007 | 48 | 4 | 21 | 0 | 54 |
|  | 32 | A/South Dakota/06/2007 | 62 | 5 | 47 | 8 | 58 |

## A/Solomon Islands/3/2006 vaccine SUMMARY TABLEVIRUSES WITH > 50% GMT REDUCTION (ADULT)

**6**

## A/Solomon Islands/3/2006 vaccine SUMMARY TABLEVIRUSES WITH > 50% GMT REDUCTION (ELDERLY)

**7**

## Antigens for serology (H3N2)

_**VACCINE STRAINS**_
**A/Wisconsin/67/2005 X161B **
**A/Hiroshima/52/2006 IVR-142 **
_**REPRESENTATIVE CURRENT STRAINS**_
**A/Brisbane/10/2007  **
**A/Henan Jinshui/147/2007**
***A/Taiwan/760/2007***
***A/Texas/37/2007 ***
***A/Toyama/119/2007***
**A/Uruguay/716/2007**

**8**

## HI ANTIBODY RESPONSES TO THE H3N2 ADULT POPULATION (UK)

| Population | N | Antigen | % Rise | Pre-
vacc
GMT | Post-
vacc
GMT | Pre-
vacc %  
HI>40 | Post- vacc %  
HI>40 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| EU | 24 | A/Wisconsin/67/2005  | 92 | 24 | 563 | 50 | 100 |
|  | 24 | A/Brisbane/10/2007 | 75 | 8 | 93 | 8 | 79 |
|  | 24 | A/Henan Jinshui/147/07 | 75 | 10 | 121 | 13 | 88 |
|  | 24 | A/Texas/37/07 | 92 | 16 | 295 | 38 | 96 |
|  | 24 | A/Uruguay/716/2007 | 71 | 10 | 147 | 17 | 83 |
| Aus | 24 | A/Wisconsin/67/2005  | 63 | 28 | 170 | 58 | 96 |
|  | 24 | A/Brisbane/10/2007 | 46 | 9 | 35 | 13 | 58 |
|  | 24 | A/Henan Jinshui/147/07 | 38 | 11 | 47 | 8 | 63 |
|  | 24 | A/Texas/37/07 | 50 | 18 | 72 | 46 | 88 |
|  | 24 | A/Uruguay/716/2007 | 54 | 11 | 53 | 17 | 67 |
| USA | 24 | A/Wisconsin/67/2005  | 50 | 95 | 457 | 79 | 100 |
|  | 24 | A/Brisbane/10/2007 | 50 | 28 | 116 | 46 | 96 |
|  | 24 | A/Henan Jinshui/147/07 | 46 | 33 | 167 | 38 | 83 |
|  | 24 | A/Texas/37/07 | 42 | 92 | 323 | 83 | 100 |
|  | 24 | A/Uruguay/716/2007 | 63 | 35 | 225 | 54 | 96 |

**9**

## HI ANTIBODY RESPONSES TO THE H3N2 ELDERLY POPULATION (UK)

| Population | N | Antigen | % Rise | Pre-
vacc
GMT | Post-
vacc
GMT | Pre-
vacc %  
HI>40 | Post- vacc %  
HI>40 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| EU | 24 | A/Wisconsin/67/2005  | 63 | 28 | 231 | 46 | 88 |
|  | 24 | A/Brisbane/10/2007 | 33 | 12 | 54 | 25 | 6 |
|  | 24 | A/Henan Jinshui/147/07 | 50 | 12 | 68 | 21 | 67 |
|  | 24 | A/Texas/37/07 | 54 | 24 | 119 | 38 | 79 |
|  | 24 | A/Uruguay/716/2007 | 46 | 16 | 102 | 29 | 67 |
| Aus | 24 | A/Wisconsin/67/2005  | 58 | 39 | 211 | 54 | 100 |
|  | 24 | A/Brisbane/10/2007 | 33 | 13 | 52 | 25 | 75 |
|  | 24 | A/Henan Jinshui/147/07 | 54 | 13 | 73 | 33 | 88 |
|  | 24 | A/Texas/37/07 | 42 | 24 | 112 | 50 | 92 |
|  | 24 | A/Uruguay/716/2007 | 42 | 16 | 78 | 29 | 88 |
| USA | 24 | A/Wisconsin/67/2005  | 54 | 66 | 267 | 58 | 100 |
|  | 24 | A/Brisbane/10/2007 | 50 | 19 | 80 | 38 | 83 |
|  | 24 | A/Henan Jinshui/147/07 | 46 | 35 | 128 | 50 | 83 |
|  | 24 | A/Texas/37/07 | 46 | 56 | 192 | 63 | 100 |
|  | 24 | A/Uruguay/716/2007 | 54 | 29 | 131 | 42 | 88 |

**10**

## HI ANTIBODY RESPONSES TO THE H3N2  PEDIATRIC   POPULATION (CDC-CBER)

**11**

|  | N | Antigen | % Rise | Pre-
vacc
GMT | Post-
vacc
GMT | Pre-
vacc %  
HI>40 | Post- vacc %  
HI>40 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| US* | 15 | A/Wisconsin/67/2005  | 93 | 5 | 76 | 0 | 80 |
|  | 15 | A/Brisbane/10/2007 | 73 | 5 | 35 | 0 | 67 |
|  | 15 | A/Uruguay/716/2007 | 60 | 5 | 15 | 0 | 27 |
|  | 15 | A/Texas/37/07 | 33 | 5 | 12 | 0 | 13 |
|  | 15 | A/Taiwan/760/2007 | 0 | 5 | 8 | 0 | 0 |
| US | 29 | A/Wisconsin/67/2005  | 86 | 8 | 48 | 17 | 69 |
|  | 29 | A/Brisbane/10/2007 | 48 | 7 | 20 | 10 | 28 |
|  | 29 | A/Uruguay/716/2007 | 28 | 7 | 14 | 10 | 10 |
|  | 29 | A/Texas/37/07 | 10 | 6 | 9 | 0 | 10 |
|  | 29 | A/Taiwan/760/2007 | 3 | 6 | 8 | 0 | 7 |
| US | 32 | A/Wisconsin/67/2005  | 93 | 12 | 269 | 28 | 100 |
|  | 32 | A/Brisbane/10/2007 | 34 | 5 | 11 | 7 | 31 |
|  | 32 | A/Uruguay/716/2007 | 48 | 6 | 15 | 10 | 38 |
|  | 32 | A/Henan Jinshui/147/07 | 38 | 6 | 12 | 10 | 31 |

## A/Wisconsin/67/2005-like VACCINESSUMMARY TABLEVIRUSES WITH > 50% GMT REDUCTION (ADULT)

**12**

## A/Wisconsin/67/2005-like VACCINESSUMMARY TABLEVIRUSES WITH > 50% GMT REDUCTION (ELDERLY)

**13**

## Antigens for serology (B)

_**VACCINE STRAIN**_
**B/Malaysia/2506/2004  (*****Vic)***
_**REPRESENTATIVE CURRENT STRAINS**_
**B/Hiroshima/320/2007  *****(Vic)***
**B/Pennsylvania/5/2007 *****(Vic)***
**B/Bangladesh/3333/2007**
**B/Delaware/1/2007**
**B/Florida/4/2007 **
***B/Norway/1760/2007***
**B/Sendai-H/114/2007**

**14**

## HI ANTIBODY RESPONSES TO B ADULT POPULATION (CDC)

|  | N | Antigen | % Rise | Pre-
vacc
GMT | Post-
vacc
GMT | Pre-
vacc %  
HI>40 | Post- vacc %  
HI>40 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| USA | 23 | B/Malaysia/2506/2004 | 54 | 27 | 220 | 46 | 100 |
|  | 23 | B/Pennsylvania/5/2007 | 58 | 29 | 254 | 42 | 10 |
|  | 24 | B/Florida/4/2006 | 46 | 65 | 240 | 49 | 100 |
|  | 24 | B/Delaware/1/2007  | 38 | 36 | 101 | 46 | 75 |
|  | 24 | B/Sendai-H114/2007 | 42 | 65 | 247 | 75 | 96 |
|  | 19 | B/Bangladesh/3333/2007  | 38 | 26 | 104 | 46 | 75 |
| EU | 24 | B/Malaysia/2506/2004 | 96 | 13 | 202 | 25 | 100 |
|  | 24 | B/Pennsylvania/5/2007 | 96 | 14 | 220 | 29 | 100 |
|  | 23 | B/Florida/4/2006 | 70 | 14 | 92 | 30 | 83 |
|  | 24 | B/Delaware/1/2007  | 54 | 8 | 30 | 8 | 50 |
|  | 24 | B/Sendai-H114/2007 | 75 | 17 | 28 | 38 | 42 |
|  | 20 | B/Bangladesh/3333/2007  | 60 | 8 | 43 | 10 | 50 |

**15**

## HI ANTIBODY RESPONSES TO B ELDERLY POPULATION (CDC)

|  | N | Antigen | % Rise | Pre-
vacc
GMT | Post-
vacc
GMT | Pre-
vacc %  
HI>40 | Post- vacc %  
HI>40 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| USA | 23 | B/Malaysia/2506/2004 | 42 | 30 | 82 | 54 | 88 |
|  | 23 | B/Pennsylvania/5/2007 | 42 | 39 | 116 | 67 | 92 |
|  | 24 | B/Florida/4/2006 | 17 | 49 | 80 | 67 | 83 |
|  | 24 | B/Delaware/1/2007  | 17 | 27 | 46 | 54 | 75 |
|  | 24 | B/Sendai-H114/2007 | 21 | 58 | 107 | 71 | 83 |
|  | 19 | B/Bangladesh/3333/2007  | 8 | 15 | 24 | 25 | 50 |
| EU | 24 | B/Malaysia/2506/2004 | 46 | 16 | 57 | 42 | 75 |
|  | 24 | B/Pennsylvania/5/2007 | 42 | 23 | 67 | 50 | 92 |
|  | 23 | B/Florida/4/2006 | 33 | 13 | 32 | 33 | 54 |
|  | 24 | B/Delaware/1/2007  | 13 | 14 | 19 | 33 | 38 |
|  | 24 | B/Sendai-H114/2007 | 31 | 9 | 19 | 23 | 42 |
|  | 20 | B/Bangladesh/3333/2007  | 4 | 12 | 17 | 35 | 39 |

**16**

## HI ANTIBODY RESPONSES TO B  PEDIATRIC   POPULATION (CDC-CBER)

**17**

|  | N | Antigen | % Rise | Pre-
vacc
GMT | Post-
vacc
GMT | Pre-
vacc %  
HI>40 | Post- vacc %  
HI>40 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| US* | 15 | B/Malaysia/2506/2004 | 77 | 5 | 55 | 0 | 77 |
|  | 15 | B/Pennsylvania/5/2007 | 69 | 5 | 58 | 0 | 77 |
|  | 14 | B/Florida/4/2006 | 15 | 5 | 9 | 0 | 15 |
|  | 15 | B/Delaware/1/2007  | 7 | 5 | 6 | 0 | 0 |
|  | 15 | B/Sendai-H114/2007 | 21 | 5 | 10 | 0 | 14 |
|  | 15 | B/Bangladesh/3333/2007  | 15 | 5 | 6 | 0 | 8 |
| US | 29 | B/Malaysia/2506/2004 | 72 | 8 | 65 | 14 | 72 |
|  | 29 | B/Pennsylvania/5/2007 | 66 | 8 | 63 | 14 | 69 |
|  | 29 | B/Florida/4/2006 | 31 | 5 | 12 | 0 | 24 |
|  | 29 | B/Delaware/1/2007  | 17 | 5 | 7 | 0 | 7 |
|  | 29 | B/Sendai-H114/2007 | 34 | 5 | 13 | 0 | 28 |
|  | 29 | B/Bangladesh/3333/2007  | 14 | 5 | 7 | 0 | 7 |
| US | 32 | B/Malaysia/2506/2004 | 48 | 4 | 22 | 0 | 34 |
|  | 32 | B/Florida/4/2006 | 7 | 4 | 5 | 0 | 0 |
|  | 32 | B/Delaware/1/2007  | 7 | 4 | 5 | 0 | 0 |
|  | 32 | B/Sendai-H114/2007 | 0 | 4 | 4 | 0 | 0 |

## B/Malaysia/2560/2004 VACCINESSUMMARY TABLEVIRUSES WITH > 50% GMT REDUCTION (ADULT)

**18**

## B/Malaysia/2560/2004 VACCINESSUMMARY TABLEVIRUSES WITH > 50% GMT REDUCTION (ELDERLY)

**19**

## Serologic conclusions

**Studies with human sera collected after immunization with current vaccines show that:**
**H1N1**
**Representative recent viruses ****were less well inhibited**** by HA antibodies**
**	**** ****to current vaccine strains (A/Solomon Islands/3/2006-like virus).   **
**H3N2**
**Representative recent viruses ****were ****less well inhibited**** by ****HA antibodies**
**	**** ****to current vaccine strain (A/Wisconsin/67/2005-like virus). **
**B**
**B/VICTORIA/2/87-lineage**
**Representative recent viruses ****were well inhibited**** by HA antibodies**
**	**** ****to current vaccine strain** (**B/Malaysia/2506/2004-like virus).**
**B/YAMAGATA/16/88-lineage**
**Representative recent viruses ****generally were less well**** inhibited by **
**HA antibodies to the current vaccine strain. **

**20**