# Presentation: 690346

## INFORMATION FOR THE VACCINES AND RELATED BIOLOGICAL

**INFORMATION FOR THE VACCINES AND RELATED BIOLOGICAL**
**PRODUCTS ADVISORY COMMITTEE,**
**CEBR, FDA**
**February 27-28, 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**

## Influenza A(H1N1)

## A[H1N1] activity,  Sept 2006 – Feb 2007

- A[H1N1] activity,  Sept 2006 – Feb 2007

## Number of influenza A(H1) viruses isolated in GISN

## New Caledonia/20/99-like     low-reactors
Australia (Oct-)	   73 [79%]		19 [21%]
US-CDC (Oct -)	 103 [87%]		16 [13%]
JP-NIID (Sept -)	      5 [83%]		  1 [17%]
UK-NIMR (Sept -)	   21 [60%]		14 [40%]
  Total		       202 [79%]       50 [21%]

- Australia (Oct-)	   73 [79%]		19 [21%]
- US-CDC (Oct -)	 103 [87%]		16 [13%]
- JP-NIID (Sept -)	      5 [83%]		  1 [17%]
- UK-NIMR (Sept -)	   21 [60%]		14 [40%]
-   Total		       202 [79%]       **50** [21%]

- Number of Influenza A(H1N1) Viruses Characterized in WHOCCs

## Slide 6

## Influenza A (H1N1) Isolates Characterized by CDC

|  | U.S.A. | North America | Europe | Asia | Cent/So America | Africa, Australia, 
New Zealand  | Total
(%) |
| --- | --- | --- | --- | --- | --- | --- | --- |
|       April 2006 – September 2006 |  |  |  |  |  |  |  |
|  A/N.Caledonia/20/99-like | 46 |  | 5 | 36 | 114 | 1 | 202 (69%) |
|  A/N.Caledon./20/99 (low) | 6 |  | 1 | 43 | 38 | 1 | 89 (31%) |
|  |  |  |  |  |  | Total | 291 |
|       October 2006 – February 2007 |  |  |  |  |  |  |  |
|  A/N.Caledonia/20/99-like | 142 | 9 |  | 4 |  |  | 155 (88%) |
|  A/N.Caledon./20/99 (low) | 8 | 1 |  | 11 | 1 |  | 21 (12%) |
|  |  |  |  |  |  | Total | 176 |
|                                        Total | 202 | 10 | 6 | 94 | 153 | 2 | 467 |

**	****	****	****	****	****	****	****	****	****	****	****	****	****Preliminary Data****	****02/22/2007**

## Evolutionary Relationships Among Influenza H1N1

-  A/Jiangxi/Anyi51/2006 ◄ Jul

**Evolutionary Relationships Among Influenza H1N1**
**HA (HA1) Genes, 2006**

- LR- low reactor to A/New Caledonia/20/1999
- Vaccine Strain
- # Egg isolate
- ____ K144E
**Serology Antigen in Boldface**
- ◄ Adamantane Resistant
- September 2006 in Blue
- October 2006 in Green
- November 2006 in Orange
- December 2006 in Pink
- January 2007 in Purple

-  NIMR A/Paris/160/2006 Dec

-  A/Maryland/6e/2006  Oct # LR

-  A/Indiana/6/2006  Oct # LR

-  A/Missouri/9/2006  Dec LR

-  A/Maryland/7/2006  Nov LR

-  A/Washington/7/2006  Dec LR

** ****A/StPetersburg/8/2006 ◄ Feb #**

** ****A/Virginia/1e/2006 ◄ Jan #**

-  A/Jiangxi/Jinxian36/2006 ◄ Jul

-  A/Hong Kong/2652/2006 ◄ Jul # LR

-  A/California/3/2006 ◄ Sep LR

-  A/Thailand/708/2006 Oct

-  NIMR A/Norway/2289/2006 Dec

-  A/Argentina/615/2006  Oct LR

-  A/Santiago/11512/2006  Sep LR

-  NIMR A/Fukushima/97/2006 Jan

** ****AUS A/SolomonIslands/3e/2006 Aug # LR**

-  A/Thailand/695/2006  Sep LR

-  A/Taiwan/785/2006  Oct LR

-  NML A/Canada/1185/2006 Nov

-  A/Washington/8/2006  Dec

-  A/Paraguay/323/2006  Jul

-  A/Wisconsin/37/2006  Dec

-  A/Georgia/26/2006  Nov #

-  A/Florida/09/2006  Dec

-  A/Oklahoma/3/2006  Dec

-  A/Venezuela/1525/2006  May LR

-  NIMR Morocco/229/2006 Dec

-  NIMR Morocco/188/2006 Dec

-  A/Guyane/14/2006  Mar

-  A/Iowa/02/2006  Dec

-  A/Massachusetts/6/2006  Nov

-  A/Alabama/20/2006  Oct

-  A/Minnesota/17/2006  Dec

-  A/Missouri/11/2006  Dec

** ****A/Florida/3e/2006  Oct #**

-  A/New Mexico/02/2006  Dec

-  A/North Carolina/10/2006  Dec

-  A/Delaware/4/2006

-  A/South Carolina/2/2006  Nov

-  A/Georgia/21/2006  Nov #

** ****A/New Caledonia/20/1999**

**Clade 1**

**Clade 2**

- V169A
- N190D/N/G/V
- W255R

- Y256F

- T90K
- Y101H
- R149K
- R212K
- T269N

- R192K
- E276K

- K144E

- S46N, R192M, A193T

- K81R
- V132T
- K144E

- P273S

- K144R

- T90V/I
- F263L

- V115I

- S46R

- A312T

- D45N
- K144E
- K149R

## Evolutionary Relationships Among Influenza A  (H1N1) Neuraminidase  Genes, 2006

-  A/Hubei/Shashi33/2006 # ◄

-  A/Guangdong/Luohu1229/2006 # ◄

-  A/Taiwan/161/2006 #

-  A/Guangdong/Futian1215/2006 # ◄

** ****A/St.Petersburg/8/2006 **# ◄ **LR**

** ****A/Virginia/1/2006 **# ◄

-  A/Jiangxi/Jinxian36/2006  ◄ LR

-  A/Indiana/6/2006 # LR

-  A/Maryland/6/2006 # LR

-  A/Taiwan/421/2006 #

** ****aus A/Solomon Islands/3/2006# LR**

-  A/Concepcion/7195/2006 # LR

-  A/Georgia/26/2006 # LR

-  A/Canada/900/2006

-  A/Kentucky/2/2006 #

-  A/Georgia/21/2006 #

** ****A/Florida/3/2006 #**

-  A/Hong Kong/29/2006 #

** ****A/New Caledonia/20/1999#**

- 0.002

**Clade 2**

**Clade 1**

- E332K
- N450D

- M23I, H64N
- G77E, 173R,
- S266T, 452G

-  G249R, T287I,
- G354D

- R130K
- E214G
- D382N

- LR: low reactor to A/New Caledonia/20/99 in HI
- #: Egg isolate
**Serology Antigen in Boldface**
- ◄: Adamantane Resistant

**Vaccine Strain**

**Evolutionary Relationships Among Influenza A  (H1N1) Neuraminidase  Genes, 2006**

## H1N1 viruses have been circulating at a low level, but sporadically in Canada, South America, and the Russian Federation. H1N1 viruses predominanted in the United States. 
Many H1N1 viruses remained antigenically-like the A/New Caledonia/20/99 vaccine strain.
An increasing proportion of recent H1N1 viruses was antigenically distinguishable from the vaccine strain. These viruses were more closely related to A/Solomon Islands/3/2006, A/Fukushima/141/2006 and A/Hong Kong/2652/2006 reference viruses.
Many of these viruses have a K144E mutation in the HA .

- Many H1N1 viruses remained antigenically-like the A/New Caledonia/20/99 vaccine strain.
- An increasing proportion of recent H1N1 viruses was antigenically distinguishable from the vaccine strain. These viruses were more closely related to A/Solomon Islands/3/2006, A/Fukushima/141/2006 and A/Hong Kong/2652/2006 reference viruses.
- Many of these viruses have a K144E mutation in the HA .

- Summary of A[H1N1] Viruses Sept 2006 - Feb 2007

## Influenza A(H3N2)

## H3H2, November 2006

## H3N2, December 2006

## H3N2, January 2007

## Number of influenza A(H3N2) viruses isolated in GISN

## Number of H3N2 Isolates Characterized in CCs

**Feb 2007 ---**

## Slide 17

## 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 | 26 | 66 | 3 | 119 (50%) |
|  A/Wisc./67/2005-like (low) | 6 |  | 10 | 47 | 12 |  | 75 (32%) |
|  |  |  |  |  |  | Total | 238 |
|      October 2006 – February 2007 |  |  |  |  |  |  |  |
|  A/Wisconsin/67/2005-like | 11 | 4 | 4 | 19 | 6 |  | 44 (41%) |
|  A/Wisc./67/2005-like (low) | 15 | 8 | 17 | 19 | 3 | 1 | 63 (59%) |
|  |  |  |  |  |  | Total | 107 |
|                                             Total | 54 | 13 | 45 | 121 | 108 | 4 | 345 |

**	****	****	****	**
**	****	****	****	****	****	****	****	****	****	****	****	****	****	****Preliminary data****	****02/22/2007**

## Slide 19

## Slide 20

## Slide 21

## Slide 22

## Slide 23

## Slide 24

## Evolutionary Relationships Among Influenza H3N2 HA (HA1) Genes, 2006

- LR- low reactor to A/Wisconsin/67/2005
- Vaccine Strain
- # Egg isolate
**Serology Antigen in Boldface**
- ◄ Adamantane Resistant
- September 2006 in Blue
- October 2006 in Green
- November 2006 in Orange
- December 2006 in Pink
- January 2007 in Purple

-  A/Canada/02/2006  Dec LR

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

-  A/Canada/28/2007  Jan LR

-  A/Lyon/22/2007 Jan

-  A/Hong Kong/3055/2006  Oct LR

-  A/Thailand/709/2006  Oct LR

-  NIMR A/Paris/478/2006 Dec

-  A/Nepal/921/2006  Jul #

-  A/Lyon/27/2007  Jan LR

-  A/Korea/122/2007  Jan LR

-  A/Gyeongnam/719/2006  Dec LR

-  A/Gyeongnam/740/2006  Dec LR

-  A/Bangladesh/1999/2006  Oct LR

-  A/Thailand/618/2006  Sep LR

-  A/Thailand/715/2006  Oct LR

-  A/Korea/69/2006 ◄ Dec LR

-  A/Hong Kong/3052/2006 ◄ Oct LR

-  A/Hawaii/06/2006 ◄ Dec LR

-  A/Korea/62/2006 Dec

-  A/Canada/32/2006  Nov LR

-  A/Hong Kong/3068/2006  Nov

-  A/Ulsan/702/2006 Dec

-  A/Wisconsin/44/2006 Dec LR

-  A/Florida/01/2007 Jan LR

-  A/New York/22/2006 ◄ Nov LR

-  A/Thailand/650/2006 ◄ Sep LR

-  A/Washington/01/2007 ◄ Jan LR

-  NIMR A/Belgium/SP1004/2007 Jan

-  A/Wisconsin/42/2006 ◄ Dec LR

-  A/Lyon Chu/01 412/2007 Jan LR

-  NML A/Canada/1182/2006 Nov

-  NIMR A/Greece/624/2006 Dec

-  A/Hong Kong/3069/2006  Nov LR

-  NIMR A/Morocco/128/2006 Nov

** ****NIMR**** A/Brisbane9/2006 Jun **

-  A/Hong Kong/3056/2006  Oct LR

-  A/Singapore/79/2006  Sep LR

-  A/Wisconsin/43/2006  Dec LR

-  A/Thailand/707/2006  Oct LR

-  A/California/7/2006  Dec

-  NIMR A/England/560/2006 Nov

-  A/El Salvador/380/2006 ◄ Sep LR

-  A/Argentina/624/2006 ◄ Oct LR

** ****A/Santiago/7981/2006 ◄ Jun #**

-  A/Mexico/2519/2006 ◄ Oct

-  NIMR A/Belgium/G0080/2007 Jan

-  A/Connecticut/1/2006 ◄ Sep LR

-  A/Thailand/692/2006 ◄ Oct LR

-  NIID A/Sendai H/F131/2006 Aug #

-  NIID A/Hiroshima/52/2005

-  A/Thailand/656/2006 ◄ Sep LR

** ****A/Wisconsin/67/2005 X161B ◄**

** ****NIID**** A/Hiroshima/33/2006 Jan #**

-  A/Canada/29/2006  Dec

-  NIMR A/Paris/458/2006 Dec

-  A/California/7/2004

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

- N6I
- K173E

- L157S

- R142G

- S45N

- N144D

- T128A

- T128A

- I67M

- G50E
- K140I

- G50E

- V112I, K173E,
- S199P,N225D

- S193F

## Evolutionary Relationships Among Influenza A  (H3N2) Neuraminidase  Genes, 2006

- LR: Low Reactor to A/Wisconsin/67/2005 in HI
- # : Egg isolate
**Serology Antigen in Boldface**

- September 2006 in Blue
- October 2006 in Green
- November 2006 in Orange
- December 2006 in Pink
- January 2007 in Purple

**Evolutionary Relationships Among Influenza A  (H3N2) Neuraminidase  Genes, 2006**

-  A/Hawaii/6/2006 LR

-  A/Korea/62/2006

** ****niid A/Hiroshima/33/2006 **

** ****A/Wisconsin/67/2005 (X161B) **

** ****A/Santiago/7981/2006 #**

-  A/Argentina/631/2006

-  A/Argentina/624/2006 LR

-  A/Canada/29/2006

-  A/Canada/23/2007 LR

-  A/Canada/02/2006 LR

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

-  A/Nepal/921/2006 #

-  A/Lyon/27/2007 LR

-  A/Gyeongnam/684/2006 LR

-  A/Korea/71/2006

-  A/Korea/122/2007 LR

-  A/Hong Kong/3055/2006 LR

-  A/Thailand/618/2006 LR

-  A/Washington/1/2007 LR

-  A/Wisconsin/42/2006 LR

-  A/Washington/11/2006 LR

-  A/Thailand/650/2006 LR

** ****A/Brisbane/9/2006 #**

-  A/Thailand/707/2006 LR

-  A/Thailand/625/2006 LR

-  A/Thailand/697/2006 LR

-  A/California/8/2006 LR

-  A/California/7/2006

-  A/Fujian/411/2002

- N43S
- S315R

- V194I
- Y310H
- L370S

## Summary - Influenza A H3N2

- Influenza activity caused by H3N2 viruses was  generally low.
- H3N2 viruses predominated and caused outbreaks in Madagascar, Canada and a number of European countries.
- Many of the viruses were antigenically closely related to A/Wisconsin/67/05 and A/Hiroshima/52/05.
- An increasing proportion of viruses was antigenically distinguishable from the vaccine viruses.
- Increased heterogeneity was observed in HA sequences from recent viruses.
- No emergent antigenic variant group was identified.

## Influenza B

## B activity Sept 2006 – Jan 2007

## Number of influenza B viruses isolated in GISN

## 			        Victoria	    Yamagata
	Australia		38 [95%]		  2 [5%] Japan		19 [95%] 		  1 [5%] UK			  2 [50%] 		  2 [50%]USA		75 [76%]		24 [24%] 
	Total		134 [82%] 		29 [18%]Low reactors	  64 [48%] 		

- 	Australia		38 [95%]		  2 [5%] Japan		19 [95%] 		  1 [5%] UK			  2 [50%] 		  2 [50%]USA		75 [76%]		24 [24%]
- 	Total		134 [82%] 		29 [18%]Low reactors	  64 [48%]

- Number of influenza B viruses characterized in WHOCCs

## Slide 32

## Slide 33

## Evolutionary Relationships Among Influenza B (Yamagata lineage) HA (HA1) Genes, 2006

- Vaccine Strain
- # Egg isolate
**Serology Antigen in Boldface**

-  B/North Carolina/02/2006 Nov

-  B/Paraguay/175/2006 Jun

-  nimr B/Parma/1/2006

-  B/Brazil/2547/2006 May

-  B/Taiwan/79/2006 Sep

-  B/Hawaii/11e/2005 #

-  B/Massachusetts/05/2006 Oct

-  nimr B/Soria/42/2006

** ****B/Michigan/2e/2006 Jan #**

-  nimr B/Norway17/2006

-  B/Peru/4020/2006 Apr LR

-  B/Peru/4135/2006 Apr

-  B/Canada/374/2006 Jan

-  B/Guyane/23/2006 May

-  nimr B/Rheinland Pfalz/8/2006

-  B/Alabama/04/2006 Sep

-  B/Venezuela/7843/2006 Mar

-  B/Peru/4051/2006 Apr

** ****B/Florida/7/2004 #**

-  B/Concepcion/8881e/2004

-  aus B/ChristChurch/33e3/2004 #

-  nimr B/Lisbon/23/2006

-  B/Argentina/622/2006 Oct

** ****B/Florida/4/2006 Nov #**

-  B/El Salvador/324/2006 Jul

-  B/Indonesia/4993/2006 Apr

-  nimr B/Norway/174/2006

-  B/Finland/767/2006 Apr LR

-  B/Alabama/01/2006 Mar

-  B/Arizona/03/2006 Apr

-  B/Hunan/Lusong1354/2006 Jun

-  B/Jilin/20/2003 #

** ****B/Shanghai/361/2002**

**Evolutionary Relationships Among Influenza B (Yamagata lineage) HA (HA1) Genes, 2006**

- M252I

- P108A

- V87I

- T34A
- V220I

- L173Q

- G230S

- N166Y
- G230D

- L 303 F

- K129N, I180V,D233A,
- M252V, G256R

- I3T
- H40Y
- L131P
- H320N

## Evolutionary Relationships Among Influenza B (Victoria lineage)

- Vaccine Strain
- # Egg isolate
**Serology Antigen in Boldface**

**Evolutionary Relationships Among Influenza B (Victoria lineage)**
**HA (HA1) Genes, 2006**

-  B/Mississippi/3/2006 Nov

-  B/Oklahoma/2/2006 Nov

-  B/Brazil/1571/2006 Oct

-  B/Taiwan/107/2006 Nov LR

-  B/Mexico/3554/2006 Nov LR

** ****B/Texas/39/2006 Nov #**

-  B/St. Petersburg/14e/2006 Mar #

-  B/Mexico/3361/2006 Nov LR

-  B/North Dakota/01/2006 Dec LR

-  AUS B/Victoria/304/2006

-  NIID B/Hiroshima/12/2006

-  NIID B/Slovakia/117/2006

-  B/Paraguay/480e/2006 Aug #

-  B/Bangladesh/967/2006 Jul # LR

-  B/Venezuela/5636/2006 Jul LR

-  B/Argentina/593/2006 Sep

-  B/Alabama/11/2006 Oct LR

-  B/Georgia/3e/2006 Nov  #

-  B/Tennessee/2/2006 Nov LR

-  B/Thailand/671/2006 Oct LR

-  NIID B/Jiangsu/xuzhougulou135/2006

-  NIID B/Chongqing/yuzhong129/2006 #

-  B/Concepcion/10662/2006 Aug LR

-  AUS B/Malaysia/46/2006

-  B/Gansu/Xihe39/2006 Jun

** ****B/Chongqing/Yuzhong131/2006 Mar #**

-  B/Yunnan/Honghei5039/2006 Jun LR

-  B/Guangxi/Xixangtang1456/2006 Jun

-  B/Mississippi/4/2006 Oct # LR

-  B/Georgia/6/2006 # Nov

-  B/Michigan/3e/2006 Mar #

-  B/Mississippi/5/2006 Nov LR

-  B/Hubei/Wujiagang180/2006 Jun #

-  B/Alabama/2/2006 #

-  B/SouthCarolina/1/2006 Nov LR

** ****AUS ****B/Malaysia/2506/2004 #**

-  B/Indonesia/2117/2006 Sep LR

** ****B/Ohio/1e/2005**** #**

-  B/Georgia/11/2006 # Nov

-  AUS B/Brisbane/32e/2002 #

-  B/Shandong/7/1997

- K48E
-  E80R
- K129N
- I190V

- K80E
- V190I

- N109K

- L58F

- T37I

## Evolutionary Relationships Among Influenza B Neuraminidase  Genes, 2006

** ****B/Chongqing/Yuzhong131/2006 #**

-  B/Wisconsin/17/2006 LR

-  B/Florida/2/2006

-  B/Venezuela/5636/2006 LR

** ****B/Texas/39/2006 #**

-  B/Mexico/3361/2006 LR

-  nimr B/Johannesburg/282/2006

-  B/North Carolina/13/2006 LR

-  B/Mississippi/4/2006 # LR

** ****B/Ohio/1/2005 #**

-  B/Arizona/02e/2006 #

-  B/Georgia/11/2006 #

-  B/Michigan/04e/2006 #

-  B/Wisconsin/31/2006 LR

-  B/South Carolina/1/2006 LR

** ****B/Malaysia/2506/2004 #**

-  B/Hong Kong/809/2006 LR

-  nimr B/Norway/174/2006

** ****B/Florida/04/2006 #**

** ****B/Michigan/2/2006 #**

-  B/Canada/374/2006

-  B/Honduras/298/2006

-  B/Peru/2985/2006 #

-  B/Shandong/7/1997

-  B/Hong Kong/1434/2002

-  B/Hong Kong/330/2001

**VIC/YAM**

**YAM/YAM**

**VIC/VIC**

**Evolutionary Relationships Among Influenza B Neuraminidase  Genes, 2006**

- LR: low reactor to B/Ohio/01/05 and B/Malaysia/2506/04 in HI
- #: Egg isolate
**Serology antigen: in boldface**

**Vaccine Strain**

## Summary Influenza B

- Influenza B viruses circulated in many countries, however outbreaks causes by influenza viruses were not reported between September 2006 and January 2007.
- Viruses of both B/Victoria/2/87 and B/Yamagata/16/88 lineages continued to circulate.
- B/Victoria/2/8 lineage viruses have predominated (82%) in recent months.
- B/Yamagata/16/88 lineage viruses were antigenically closely related to B/Florida/7/2004, B/Egypt/144/2005 or B/Michigan/2/2006.
- Most B/Victoria/2/87 lineage viruses were antigenically closely related to B/Malaysia/2506/2004.

## Number of egg-grown viruses by fiscal year (Oct 1 – Sep 30)

**Number of egg-grown viruses by fiscal year ****(Oct 1 – Sep 30)**

*** October 1, 2006 – February 25, 2007**

## Human Serology

## Slide 40

## Slide 41

## Slide 42

## Slide 43

## Slide 44

## Slide 45

## Slide 46

## Slide 47

## Slide 48