# Presentation: 188445

## INFORMATION FOR THE VRBPAC, CEBR, FDAMay 16, 2007

**INFORMATION FOR THE VRBPAC, CEBR, FDA****May 16, 2007**

**WHO Collaborating Center for Surveillance,**
**Epidemiology and Control of Influenza**

**Influenza Division**
**National Center for Immunization and Respiratory Diseases**
**Coordinating Center for Infectious Diseases**
**Centers for Disease Control and Prevention**
**Atlanta, GA 30333**

**Alexander Klimov, PhD., ScD**
**Deputy Director**

## Evolutionary Relationships Among Influenza H3N2 HA (HA1), 2007

-  A/Texas/04/2007 ◄ Jan

-  A/Georgia/02/2007 ◄ Jan LR

-  A/Texas/03/2007  Jan LR

-  nor A/Norway/365/2007 Feb

-  A/Missouri/01/2007 ◄ Jan LR

-  nor A/Norway/136/2007 Jan

-  A/Canada/366/2007 ◄ Jan LR

-  A/Colorado/03/2007 ◄ Jan

** ****A/Lyon/1331/2006 ◄ Dec LR REFAG**

-  A/Lyon Chu/01 412/2007 ◄ Jan LR

-  A/North Carolina/01/2007 ◄ Jan LR

-  A/New Mexico/03/2007  Jan

-  nor A/Norway/415/2007 Feb

-  A/Missouri/02/2007 ◄ Feb LR

-  A/Missouri/03/2007 ◄ Feb LR

-  A/Canada/111/2007 ◄ Jan LR

-  A/North Carolina/02/2007 ◄ Jan LR

-  A/Colorado/04/2007 ◄ Jan LR

-  A/Korea/7236/2007 ◄ Jan LR

-  A/Indiana/01/2007 ◄ Jan

-  A/Indiana/02/2007 ◄ Feb

-  A/New Jersey/03/2007 ◄ LR

** ****A/Hawaii/08/2006 ◄ Dec LR REFAG**

-  A/Idaho/01/2007 ◄ Jan LR

-  A/Idaho/02/2007 ◄ Jan LR

-  A/Idaho/03/2007 ◄ LR

-  A/New York/02/2007 ◄ Jan LR

-  A/Washington/01/2007 ◄ Jan LR

-  A/New Mexico/01/2007  Jan LR

-  nor A/Norway/405/2007 Feb

-  A/New Mexico/02/2007  Jan

- A/Wisconsin/03/2007

- A/Wisconsin/03/2007 #

-  A/Brazil/1898/2006 ◄ Jun #

-  A/Santiago/7981/2006 ◄ Jun #

** ****nimr A/Brisbane9/2006 Jun **

-  A/Wyoming/02/2006 ◄ Feb #

** ****A/Honduras/93/2005 ◄ REFAG LR**

-  nimr A/Belgium/G0080/2007 Jan

** ****A/Kentucky/03/2006 ◄ # REFAG LR**

-  A/Florida/02/2007 ◄ Jan LR

** ****A/Florida/2e/2006 ◄ Jan #**

** ****A/Wisconsin/67/2005 X161B ◄**

-  A/Peru/5102/2006 ◄ Jul #

-  A/Peru/5107/2006 ◄ Jul #

-  aus A/Thailand/29/2007

-  A/Korea/122/2007  Jan LR

-  A/Korea/7123/2007  Jan LR

-  niid A/Shizuoka/18/2007

-  aus A/Victoria/500/2007

-  A/Texas/01/2007  Jan

-  A/New Jersey/02/2007  Jan LR

-  A/Lyon/27/2007 sen Jan LR

-  A/Canada/267/2007  Jan LR

-  A/Indiana/03/2007  Jan LR

-  A/Nepal/1445/2006  Jul LR

** ****A/Nepal/921/2006  Jul #**

-  A/Lyon/22/2007 sen Jan

-  A/Canada/125/2007  Jan

-  A/Canada/315/2007  Jan

-  A/Canada/85/2007  Jan LR

-  A/Canada/264/2007  Jan

-  A/New Jersey/05/2007  Feb LR

-  A/New York/03/2007  Feb LR

** ****A/Canada/1212/2006  Dec LR**

-  A/Wisconsin/02/2007  Jan LR

-  A/Korea/7210/2007 ◄ Jan

-  bafb A/Korea/210/2007

-  niid A/Osaka/1/2007

-  niid A/Kochi/1/2007

-  niid A/Yamaguchi/1/2007

-  bafb A/Washington/7361/2007

-  niid A/Ishikawa/1/2007

-  A/Japan/7288/2007 ◄ Jan LR

-  A/Japan/7217/2007 ◄ Jan

-  niid A/Sendai/12/2007

-  A/Florida/01/2007 ◄ Jan LR

-  niid A/Mie/1/2007

-  A/Canada/305/2007 ◄ Jan LR

-  bafb A/California/7383/2007

** ****A/Hong Kong/2831/2005 ◄ REFAG**

-  niid A/Hiroshima/33/2006 Jan #

** ****A/Ukraine/13/2006  REFAG LR**

** ****A/California/07/2004**

-  A/Bangladesh/1817/2005  May #

** ****A/New York/55e/2004**

-  A/Fujian/411/2002

- 0.002

- LR- low reactor to A/Wisconsin/67/2005*
- * Some viruses may be low avid
**Vaccine Strain**
- # Egg isolate
- Reference Antigens  in Boldface
- ◄ Adamantane Resistant

- Brisbane-like

- Nepal-like

- 122D, 138S, 156Q,
- 186V, 223I

- G50E

- K140I

- I192V

- K173E

- N6I
- R142G
- L157S
- K173E

- T128A
- Loss of Gly motif  at 126

- R142G
- N144D
- Loss of Gly motif  at 144

- S124R
- Loss of Gly motif  at 124

**Evolutionary Relationships Among Influenza H3N2 HA (HA1), 2007**

## Genetic Analysis of 2006-07 H3N2 Influenza Viruses

** ****A/Brisbane/9/2006:**** **
** ****~52% of the recent isolates **
** ****67% - reduced titers against ferret antiserum* raised to A/Wisconsin/67/2005 in HI test**
*** ****Some may be low avid viruses**** **
** ****Egg isolate A/Wisconsin/03/2007 – reassortant in progress**
** **
**  ****A/Nepal/921/2006:**
** ****~46% of recent isolates. **
** ****66% - reduced titers against ferret antiserum* raised to A/Wisconsin/67/2005 in HI**
*** ****Some may be low avid viruses**
** ****The only egg isolate – A/Nepal/921/2006 **
** ****X165 reassortant from this virus has been created**

**Genetic Analysis of 2006-07 H3N2 Influenza Viruses**

## Influenza A(H3N2) Isolates Characterized by CDC

|  | U.S.A. | North America | Europe | Asia | Cent/So America | Africa, Australia, 
New Zealand  | Total
(%) |
| --- | --- | --- | --- | --- | --- | --- | --- |
|      April 2006 – September 2006 |  |  |  |  |  |  |  |
| A/California/07/2004-like | 4 |  | 9 | 10 | 21 |  | 44 (18%) |
| A/Wisconsin/67/2005-like | 18 | 1 | 5 | 27 | 66 | 3 | 120 (51%) |
| A/Wisconsin/67/2005-like (low)* | 6 |  | 10 | 46 | 12 |  | 74 (31%) |
|  |  |  |  |  |  | Total | 238 |
|      October 2006 – February 2007 |  |  |  |  |  |  |  |
| A/Wisconsin/67/2005-like | 41 | 22 | 6 | 23 | 5 | 1 | 98 (29%) |
| A/Wisconsin/67/2005-like (low)* | 116 | 62 | 27 | 24 | 8 | 5 | 242 (71%) |
|  |  |  |  |  |  | Total | 340 |
| Total | 185 | 95 | 57 | 130 | 112 | 8 | 638 |

**	****	****	****	****	****	****	****	****	****	****	****	****	****Preliminary data****	****05/16/2007**
*** Some may be low-avid viruses.**

**Influenza A(H3N2) Isolates Characterized by CDC**

## HI REACTIONS OF INFLUENZA H3 VIRUSES 

**HI REACTIONS OF INFLUENZA H3 VIRUSES **

## HI REACTIONS OF INFLUENZA H3 VIRUSES 

**HI REACTIONS OF INFLUENZA H3 VIRUSES **

## HI and MN Antibody Response of 2006-07 Vaccine Recipients

**HI and MN Antibody Response of 2006-07 Vaccine Recipients**
**to H3N2 viruses**

## MN Antibody Response of 2006-07 Vaccine Recipients to H3N2 viruses

**MN Antibody Response of 2006-07 Vaccine Recipients to H3N2 viruses**

## Conclusions

**Two major genetic groups in the H3 HA: ****	****A/Nepal/921/2006 and A/Brisbane/9/2006**
**HI tests using ferret antisera to the A/Nepal/921/06 reassortant virus indicates that this virus is not a superior vaccine candidate when compared with the A/Wisconsin vaccine strain**
**Although post infection ferret antisera to Nepal/921 and Canada/1212 cover recent H3N2 viruses somewhat better than antiserum to A/Wisconsin/67/2005-wt virus, there is not a reciprocal two way difference in antibody titers when these three viruses are compared**
**Microneutralization tests conducted with postinfection ferret serum (data not shown) also indicated that only a one way difference and not a two way reciprocal difference could be detected between Wisconsin-like and Nepal-like viruses. **

## Conclusions (cont.)

**     ****vaccination sera are higher than HI titers (as expected)**
**6.  There is not consistent reductions in **
**     ****the serum antibodies from US adults when comparing the **
**     ****homologous titer using the Wisconsin strain with that **
**     ****obtained with Nepal-like viruses tested**
**  ****We do see reductions, however, in the serum antibody titers**
**     ****in elderly and children when comparing the Nepal-like viruses **
**     ****with the homologous Wisconsin vaccine strain**
**  ****Over all conclusion: we cannot detect a reciprocal two way **
**     ****difference in HAI or microneutralization titers for the Nepal-**
**     ****like viruses and the ferret antiserum to the reassortant made**
**     ****using the Nepal/921 virus is not superior in covering recent **
**     ****strains. Therefore, these results are consistent with the**
**     ****February decisions to recommend the A/Wisconsin/67/2005**
**     ****viruses be in the influenza vaccine for 2007-08 influenza**
**     ****season**

**Conclusions (cont.)**