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Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta, GA 30333 Bethesda, MD February 20, 2003 INFORMATION FOR THE VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE, CBER, FDA WHO COLLABORATING CENTER FOR SURVEILLANCE, EPIDEMIOLOGY AND CONTROL OF INFLUENZA

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Page 1: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Influenza BranchDivision of Viral and Rickettsial DiseasesNational Center for Infectious Diseases

Centers for Disease Control and PreventionAtlanta, GA 30333

Bethesda, MD

February 20, 2003

INFORMATION FOR THE VACCINES AND RELATED BIOLOGICALPRODUCTS ADVISORY COMMITTEE, CBER, FDA

WHO COLLABORATING CENTER FOR SURVEILLANCE,EPIDEMIOLOGY AND CONTROL OF INFLUENZA

Page 2: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,
Page 3: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

U.S. SURVEILLANCE

Page 4: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

WHO/NREVSS Collaborating Laboratories National Summary, 2002-03

0

100

200

300

400

500

40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18 20

Week

Nu

mb

er

of

Iso

late

s

0

5

10

15

20

25

30

Pe

rce

nt

Po

sit

ive

A(H3N2)

A(H1N1) and A(H1N2)

A(Unsubtyped)

B

Percent Positive

Page 5: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Percentage of Visits for ILI Reported by Sentinel ProvidersNational Summary, 2002-03

0

1

2

3

4

5

6

40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18 20

Week

% o

f V

isit

s f

or

ILI

Page 6: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Weekly Influenza Activity Estimates Reportedby State & Territorial Epidemiologists

No Report Sporadic Regional Widespread No Activity

Week ending February 8, 2003 - Week 6

Page 7: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Pneumonia and Influenza Mortality for 122 U.S. CitiesWeek Ending 02/08/03

4

6

8

10

12

Weeks

% o

f All

Dea

ths D

ue to

P&

I

1999 2000 2001 2002

“Epidemic” Threshold

Seasonal Baseline

10 20 30 40 50 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50 10

2003

Page 8: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

INFLUENZA A(H1) VIRUSES

Page 9: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA H1 VIRUSES

STRAIN DESIGNATION REFERENCE FERRET ANTISERAA B C D Date

REFERENCE ANTIGENS BJ/262 NC/20 HI/10 HI/15 collected Passage NA

1 A/BEIJING/262/95 640 320 320 40 01/09/95 E3/E3 N12 A/NEW CALEDONIA/20/99* 160 320 160 80 06/09/99 E4/E1 N13 A/HAWAII/10/2002 80 160 320 40 03/22/02 E3 N24 A/HAWAII/15/2001 20 40 20 160 02/17/01 M2/C3 N1

TEST ANTIGENS

5 A/MASSACHUSETTS/5/2002* 160 320 160 80 12/06/02 X/C1 N16 A/WISCONSIN/12/2002 160 640 320 160 12/03/02 C1/C1 N17 A/TEXAS/49/2002 160 320 160 80 11/25/02 M1/C1 N18 A/NEW JERSEY/05/2002 160 320 160 40 UNKN MX/C1 N19 A/CANADA/641/2002 320 320 640 40 11/20/02 X/C1 N210 A/CANADA/649/2002* 160 320 640 40 12/04/02 X/C1 N211 A/DELAWARE/01/2002 320 640 640 40 12/29/02 M2/C1 N212 A/PENNSYLVANIA/01/2003 640 640 1280 40 01/16/03 X/C1 N213 A/NEW YORK/01/2003 320 640 320 80 01/02/03 M1/C1 N114 A/NEW YORK/07/2003 320 640 640 40 01/07/03 X1/C1 N215 A/TEXAS/02/2003 80 320 160 80 01/05/03 M1/C1 N116 A/WASHINGTON/08/2002 160 320 1280 40 12/31/02 M1/C1 N217 A/MICHIGAN/208/2003 80 320 160 80 01/21/03 M1/C1 N118 A/MICHIGAN/236/2003 160 320 320 40 05/05/03 M1/C1 N219 A/PERU/3090/2002* 160 80 20 160 09/08/02 X/C1 N120 A/PERU/3064/2002 20 80 20 80 08/14/02 X/C1 N1

* Serology antigens

Page 10: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Influenza A(H1) Isolates Characterized by CDC

U.S.A. North America

Europe Asia Cent/So America

Africa, Australia,

New Zealand

Total (%)

April 2002 - September 2002

A/N.Caledonia/20/99-like 4 2 7 37 1 51 (76%)

A/N.Caledon./20/99-like (low) 2 14 16 (24%)

A/Johannesburg/82/96-like

Total 67

October 2002 - February 2003

A/N.Caledonia/20/99-like 47 9 1 57 (97%)

A/N.Caledon./20/99-like (low) 1 1 2 (3%)

A/Johannesburg/82/96-like

Total 59

Total 54 12 7 51 2 126

Preliminary Data 02/18/2003

Page 11: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Influenza A(H1N1) & A(H1N2) Isolates Identified by CDC

U.S.A. North America

Europe Asia Cent/So America

Africa, Australia,

New Zealand

Total (%)

April 2002 - September 2002

H1N1 5 2 9 51 1 68 (97%)

H1N2 1 1 2 (3%)

Total 70

October 2002 - March 2003

H1N1 61 1 3 1 66 (69%)

H1N2 21 9 30 (31%)

Total 96

Total 88 12 12 52 2 166

Preliminary Data 02/18/2003

Page 12: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Canada/649/2002*Michigan/2/2003

New York/3/2003Washington/8/2002

Canada/642/2002(LR)North Carolina/7/2002

Peru/3084/2002New York/2/2003Pennsylvania/1/2003

New York/26/2002Hawaii/10/2002#

South Dakota/2/2002Jilin/5/2002#

Florida/7/2002Peru/3090/2002(LR)*

Colombia/3575/2002Wuhan/6/2002

Neimongol/31/2002#Neimongol/43/2002#

Hong Kong/841/2002Alaska/1/2002Texas/49/2002

Hubei/18/2002(LR)#Sichuan/656/2002

Mexico/935/2002Wisconsin/12/2002

Guatemala/48/2002Texas/52/2002

Guizhou/198/2002Massachussetts/5/2002*

Oklahoma/3/2002Texas/1/2003

bafbKorea/1136/2002New Jersey/5/2002Michigan/1/2003

New York/1/2003Chile/10751/2002#

Chile/8196/2002#Chile/13309/2002#

Chile/8829/2002(LR)#nihjAkita/25/2002#

Chile/8885/2002(LR)#Alaska/3/2002

Arizona/13/2002Yamaguchi/12/2002

Georgia/8/2002Hawaii/15/2001(LR)

Russia/2187/2002(LR)#New Caledonia/20/99#*

E125bG, K166M

D275G

E82G

V169A

W255R

A193T, A218T, V178I

T96A

H1N

2

* serology antigen# egg isolate(LR) low reactor to A/New Caledonia/20/99vaccine strain

EVOLUTIONARY RELATIONSHIPS AMONG INFLUENZA A(H1) HA1 GENES

Page 13: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

NEURAMINIDASE INHIBITION TEST OF INFLUENZA N1 VIRUSES

STRAIN DESIGNATION FERRET ANTISERAA B C Date

REFERENCE ANTIGENS New Cal/20/99 Fuji/156/00 Neim/52/02 collected

1 A/New Caledonia/20/99 1280 1280 1280 06/09/992 A/Fujian/156/2000 1280 2560 1280 08/25/003 A/Neimonggu/52/2002 1280 2560 1280 01/25/024 A/Johannesburg/82/96 320 640 480 1996

TEST ANTIGENS

5 A/Colombia/3059/2002 1280 2560 2560 09/13/026 A/Guizhou/198/2002 2560 2560 1280 06/18/027 A/Wisconsin/12/2002 1280 1280 2560 12/03/028 A/Texas/48/2002 1280 1280 1280 11/14/02

Page 14: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

NEURAMINIDASE INHIBITION TEST OF INFLUENZA N2 VIRUSES

STRAIN DESIGNATION FERRET ANTISERAA B C D Date

REFERENCE ANIGENS PN/2007/99 Chile/6416/01 HI/10/02 New Cal/20/99 collected

1 A/Panama/2007/99 (H3N2) 320 80 40 <10 07/12/992 A/Chile/6416/2001(H3N2) 160 320 80 <10 06/14/013 A/Shenzhen/499/2001(H3N2) 320 80 80 <10 05/22/004 A/Hawaii/10/2001(H1N2) 40 40 320 <10 03/22/025 A/New Caledonia/20/99 (H1N1) <10 <10 <10 1280 09/01/99

TEST ANIGENS

6 A/New York/28/2002 (H3N2) 320 320 120 <10 10/12/027 A/Fujian/411/2002 (H3N2) 160 160 80 <10 08/11/028 A/Peru/3084/2002 (H1N2) 80 80 320 <10 08/13/029 A/Canada/638/2002 (H1N2) 80 80 320 <10 11/19/02

Page 15: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Hong Kong/1252/2000Wuhan/251/2000#

Hong Kong/241/2000Wuhan/292/2000#

Russia/11/2001Shenzhen/201/2000#Hawaii/18/99

Fujian/156/2000#Hawaii/1/2000

Nanchang/8/2000#nimr-Hong Kong/1799/2000

Taiwan/1486/2001Hubei/288/2001*#

Hong Kong/747/2001*Brazil/821/2001*

Pusan/124/99New Caledonia/20/99*#

aus-New Caledonia/11/2000nimr-Ishikawa/42/98

Colorado/2/2001Hawaii/15/2001*

Bangkok/255/2001*#Washington/6/2001

nimr-Asuncion/1041/2000nimr-Brazil/202/2000

Bangkok/163/2000California/26/99

Peru/1261/99Peru/1798/99

nimr-Moscow/17/98nimr-Hong Kong/4859/98

Beijing/262/95New York/14/2000

Colorado/1/2001Chile/5255/2000

Chile/5724/2000nimr-Oslo/1734/98

Bayern/7/95Taiwan/1/86

V75IR222QD344N

D386N

Vaccine strain

*Serology Antigen# Egg isolate

10 nucleotides

EVOLUTIONARY RELATIONSHIPS AMONG INFLUENZA A(N1) NA GENES

Page 16: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Summary: Influenza A(H1N1 and H1N2) Viruses

• Since last winter, H1N1 and H1N2 viruses have been reported primarily from the Americas (Canada, Chile and the U.S.).

• Most (>95%) of recent H1 viruses have HAs that are antigenically and genetically similar to that of the current vaccine strain, A/New Caledonia/20/99

• The NAs of current H1N1 viruses are similar antigenically and genetically to the N1 of A/New Caledonia/20/99

• The NAs of current H1N2 viruses are similar to to those of currently circulating H3N2 viruses

Page 17: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

INFLUENZA A(H3N2) VIRUSES

Page 18: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA H3 VIRUSES

STRAIN DESIGNATION REFERENCE FERRET ANTISERAA B C D E F Date Passage

REFERENCE ANTIGENS SYD/5 MOS/10 PN/2007 HK/1550 NY/55 FUJ/411 collected

1 A/SYDNEY/05/97 640 10 320 320 640 40 06/23/97 CK2E2/E22 A/MOSCOW/10/99 320 640 320 320 640 40 01/15/99 E2/E23 A/PANAMA/2007/99* 160 160 320 320 640 80 07/12/99 E54 A/HONG KONG/1550/2002 640 320 640 640 1280 80 01/19/02 E55 A/NEW YORK/55/2001 320 320 640 320 1280 20 11/22/01 E46 A/GUANGZHOU/405/2002 40 40 160 160 160 1280 05/21/02 C2/C4

TEST ANTIGENS

7 A/NEW JERSEY/04/2002 640 1280 640 1280 1280 160 11/04/02 E28 A/THAILAND/1170/02 320 320 640 640 1280 160 10/21/02 X/C19 A/EGYPT/919441/2002 320 1280 640 640 1280 80 11/07/02 C2/C1

10 A/DAKAR/50/02 320 320 640 320 1280 80 10/30/02 CXC1/C111 A/EGYPT/919441/2002 320 640 640 640 1280 80 11/07/02 C2/C112 A/NEW JERSEY/4/2002* 160 320 320 640 640 n.d. 11/04/02 X/C413 A/ALASKA/4/2002 160 160 320 320 320 1280 12/02/02 X/C114 A/THAILAND/1169/2002 160 640 320 320 640 160 10/17/02 X/C115 A/ALASKA/4/2002 160 160 320 320 320 1280 12/02/02 X/C116 A/TEXAS/53/2002 160 160 320 320 320 2560 12/18/02 M1/C117 A/ENGLAND/455/2002 320 160 320 320 640 320 12/30/02 C1/C218 A/HAWAII/20/2002 80 160 160 320 160 640 12/04/02 C1/C219 A/GUAM/228/2002* 80 320 160 640 320 n.d. 10/26/02 X/C220 A/OSAKA/c70/2002 40 80 80 320 160 640 11/15/02 C2/C121 A/BEIJING/301/2002 40 160 80 80 160 640 12/20/02 C1/C122 A/KOREA/770/2002* 40 80 80 160 80 n.d. 12/02/02 X/C323 A/OSAKA-C/70/02 40 160 80 320 160 640 11/15/02 C2/C124 A/MEMPHIS/3/2003 40 40 80 80 80 320 01/21/03 C1/C125 A/EGYPT/919505/2002 40 80 80 320 160 80 11/16/02 C1/C226 A/BEIJING/290/2002 20 160 40 80 80 320 12/19/02 C1/C127 A/SHIGA/41/02 20 80 40 160 80 80 11/25/02 C1/C128 A/HAWAII/14/2002 20 40 40 40 40 640 12/24/02 M2/C1

* Serology antigens Courier - changes at aa 155+156

Page 19: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Influenza A(H3N2) Isolates Characterized by CDC

U.S.A. North America

Europe Asia Cent/So America

Africa, Australia,

New Zealand

Total (%)

April 2002 - September 2002

A/Panama/2007/99-like 15 1 3 108 27 7 161 (89%)

A/Panama/2007/99-like (low) 8 3 9 20 (11%)

Total 181

October 2002 - February 2003

A/Panama/2007/99-like 25 4 4 37 7 77 (70%)

A/Panama/2007/99-like (low) 8 24 1 33 (30%)

Total 110

Total 48 5 7 177 30 24 291 Preliminary Data 02/18/2003

Page 20: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Moscow/5/2000 #

Panama/2007/99 # **Fujian/140/2000 #

Beijing/144/2001Hong Kong/1550/2002 #

Moscow/10/99 #Sydney/5/97 #

R 50 GE 83 KV 202 I

W 222 RG 225 D

10 nucleotides

NIMR-Madagascar/66213/2002New York/28/2002

Aus-Victoria/241/2002Hawaii/4/2002

New York/55/2001 (LR)Utah/6/2002

NIID-Fukuoka/15/2002Aus-Sydney/23/2002

Hawaii/11/2002Louisiana/2/2002

New York/21/2002England/449/2002

North Carolina/8/2002Chile/6416/2001 #

Turkey/1035/2002NIMR-Dakar/50/2002 **

Brazil/1727/2002 (LR) #Brazil/2458/2002

Connecticut/1/2002Illinois/1/2002

Texas/4/2002Aus-Bangkok/109/2002 (LR) #

Washington/3/2002Wisconsin/17/2001Oklahoma/2/2002

Arizona/1/2002England/1/2003

NIID-Akita/69/2002 #

A 106 VN 144 D

A 304 P

Aus-Brisbane/5/2002 (LR) #NIID-Hyogo/3/2002

Aus-Perth/200/2002 (LR) #

Zhejiang/8/2002 (LR)India/25502/2002

Hubei/61/2002 (LR)Guangzhou/405/2002

Q 156 H

L 25 IH 75 QH 155 T

A 131 T

Hawaii/13/2002Aus-Taiwan/8/2002

NIID-Shiga/41/2002Can-Canada/rv6222/2002

Aus-Singapore/44/2002 (LR)Hong Kong/1554/2002

Hong Kong/1143/2002 (LR)Philippines/160283/2002 (LR)

Taiwan/1521/2002 (LR)Guam/228/2002 (LR)NIMR-Switzerland/7494/2002

New Jersey/4/2002 (LR) **NIMR-Egypt/151/2002

Beijing/178/2002 (LR)Fujian/411/2002 **Anhui/550/2002 (LR)

Beijing/301/2002 (LR)

Japan/910/2002 (LR)Alaska/4/2002California/9/2002Korea/770/2002 (LR)Hunan/407/2002

Hawaii/19/2002 (LR)Massachusetts/1/2003 (LR)

NIID-Toyama/29/2002PHLS-England/448/2002 (LR)

Memphis/4/2003 (LR)Memphis/1/2003 (LR)

Washington/3/2003NIID-Osaka-c/70/2002

NIID-Ishikawa/102/2002 **Georgia/1/2003 (LR)

BAFB-Korea/172/2003

Vaccine StrainEgg-Grown Isolate #Serology Antigen **Low Reactor (LR)

EVOLUTIONARY RELATIONSHIPS AMONG INFLUENZA A(H3) HA1 GENES

Page 21: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

NEURAMINIDASE INHIBITION TEST OF INFLUENZA N2 VIRUSES

STRAIN DESIGNATION FERRET ANTISERAA B C Date

REFERENCE ANIGENS PN/2007/99 Chile/6416/01 Shzh/499/00 collected

1 A/Panama/2007/99 (H3N2) 320 80 80 07/12/992 A/Chile/6416/2001(H3N2) 160 320 160 06/14/013 A/Shenzhen/499/2001(H3N2) 320 80 320 05/22/00

TEST ANIGENS

4 A/New York/28/2002 (H3N2) 320 320 320 10/12/025 A/Fujian/411/2002 (H3N2) 160 160 160 08/11/02

Page 22: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

EVOLUTIONARY RELATIONSHIPS AMONG INFLUENZA A(N2) NA GENESWuhan/396/2001

Wuhan/388/2001CNIC/114/2001Hong Kong/1307/2001

Guangzhou/1191/2001Singapore/54/2001

Shenzhen/499/2000#Hong Kong/1269/2001

Singapore/41/2001Nepal/1610/2001

Singapore/15/2001*Thailand/80891/2001

Hawaii/23/2001Wisconsin/12/2001

nimr-Moscow/10/2001#Hong Kong/762/2001*

Hong Kong/648/2001*#Hawaii/21/2001*Philippine/78890/2001*

Hawaii/29/2001Alaska/14/2001*

Alaska/8/2001Chile/6416/2001*#

Argentina/302/2001Argentina/10/2001

Argentina/3758/2001#Argentina/3759/2001*#

Massachusetts/2/2001North Carolina/1/2001

South Australia/102/2001*Florida/6/2001

Panama/2007/99*#Sydney/5/97

A18S, L23F, V307I

V30T, C42F

G414S

S332F, Q432E

K172R

10 nucleotides*Serology antigen# Egg isolate

Vaccine Strain

Page 23: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Summary: Influenza A(H3N2) Viruses

• H3N2 viruses have caused recent outbreaks in Japan, Korea and China

• An increasing proportion of recent H3N2 isolates are not well inhibited by post-infecton and post-immunization antiserum

• H3N2 viruses with aa changes at 155 and 156 (Site B) tend to be poorly inhibited by antibodies to the vaccine virus

• Low reacting viruses with aa changes at 155 and 156 have been detected in Asia, Europe and the Americas

Page 24: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

INFLUENZA B VIRUSES

Page 25: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA TYPE B VIRUSES

STRAIN DESIGNATION REFERENCE FERRET ANTISERAA B C D E Date

REFERENCE ANTIGENS SIC/379 SHI/15 SHA/07 HK/330 BRI/32 collected Passage HA-NA

1 B/SICHUAN/379/99 640 640 20 5 40 12/02/99 E2/E4 Sic-Sic2 B/SHIZUOKA/15/2001 320 320 10 5 10 01/17/01 E3/E2 Sic-Sic3 B/SHANDONG/7/97* 10 5 640 320 640 11/03/97 E4/E3 SH-Vic4 B/HONG KONG/330/2001* 10 5 320 320 640 04/09/01 E3 HK-Vic5 B/BRISBANE/32/2002* 10 5 320 160 640 07/02/02 E2/E4 SH-Sic

TEST ANTIGENS

6 B/SHANGHAI/361/2002* 640 640 20 20 20 06/12/02 E2/E1 Sic-Sic7 B/TEXAS/04/2003 80 160 5 5 5 01/14/03 M1/C1 Har-Sic8 B/SHANGHAI/720/2002 320 160 20 5 10 11/27/02 C1E1/E3 Har-Sic9 B/HONG KONG/1434/2002* 10 5 640 640 1280 01/15/02 E4 HK-Vic10 B/OKLAHOMA/03/2002 5 5 160 320 640 11/25/02 X1/C1 SH-Sic11 B/MISSOURI/10/2003 20 5 320 320 1280 01/09/03 X/C1 SH-Sic12 B/IOWA/03/2003 5 5 160 320 640 01/24/03 X1/C1 SH-Sic13 B/NEVADA/05/2002 10 5 320 320 640 12/17/02 X/C2 SH-Sic14 B/GUANGZHOU/992/2002 5 5 320 320 640 11/20/02 C2/C2 SH-Sic15 B/JAPAN/147/2002 5 5 160 160 640 12/24/02 X/C1 HK-Sic16 B/NEW JERSEY/01/2003 5 5 160 160 320 01/27/03 MX/C1 SH-Sic17 B/SOUTH DAKOTA/01/2003 5 5 160 160 320 01/14/03 M1/C1 SH-Sic18 B/TIANJIN/130/2002 5 5 160 160 640 12/18/02 C1/C1 SH-Sic19 B/TIANJIN/192/2002 10 5 160 160 640 12/16/02 C1/C1 SH-Sic20 B/TIANJIN/189/2002 5 5 160 160 640 12/17/02 C1/C1 SH-Sic21 B/BEIJING/171/2002 5 5 80 160 320 11/22/02 C1/C1 SH-Sic22 B/NEVADA/01/2003 5 5 80 80 160 01/18/03 M1/C1 SH-Sic23 B/NEW YORK/01/2003 5 5 80 80 320 01/04/03 X1/C1 SH-Sic24 B/TEXAS/07/2003 5 5 80 80 320 01/21/03 M1/C1 SH-Sic25 B/WASHINGTON/01/2003 5 5 80 80 160 01/15/03 X/C1 SH-Sic26 B/IOWA/02/2003 5 5 80 80 320 01/24/03 X1/C1 SH-Sic27 B/S.CAROLINA/01/2003 5 5 80 80 320 01/16/03 X1/C1 SH-Sic28 B/TEXAS/57/2002* 5 5 160 80 320 12/04/02 M1/C1 SH-Sic

* Serology antigens

Page 26: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Influenza B Isolates Characterized by CDC

U.S.A. North America

Europe Asia Cent/So America

Africa, Australia,

New Zealand

Total (%)

April 2002 - September 2002

B/Hong Kong/330/2001-like 56 22 57 17 152 (43%)

B/HK/330/2001-like (low) 41 68 48 16 173 (49%)

B/Sichuan/379/99-like 2 10 2 14 (4%)

B/Sichuan/379/99 (low) 1 6 8 15 (4%)

Total 354

October 2002 - February 2003

B/Hong Kong/330/2001-like 39 3 56 1 99 (54%)

B/HK/330/2001-like (low) 50 1 21 72 (40%)

B/Sichuan/379/99-like 2 4 6 (3%)

B/Sichuan/379/99 (low) 1 3 2 6 (3%)

Total 183

Total 190 1 3 188 121 34 537

Preliminary Data 02/18/2003

Page 27: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Currently Circulating Type B HA Lineages

Hong Kong/330/2001

25 nucleotides

Victoria Lineage

Yamagata Lineage

Page 28: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

EVOLUTIONARY RELATIONSHIPS AMONG INFLUENZA B HA1 GENES (YAMAGATA LINEAGE)

Egg-Grown Isolate #Serology Antigen **Low Reactor (LR)

NIID-Fukushima/24/2002Harbin/7/94 #

Taiwan/143999/2002 (LR)NIMR-Madagascar/65186/2002

Moscow/16/2002 #NIID-Astrakhan/10/2002 #

California/2/2002NIID-Ulan Ude/4/2002 #Russia/4/2002 (LR) #

NIID-Yunnan/406/2001 #Colorado/3/2002 (LR)

Fujian/407/2001 #NIMR-St. Petersburg/1/2002NIMR-Finland/141/2002

Nevada/1/2002NIMR-Hong Kong/293/2002

NIID-Yunnan/8/2002 #Yunnan/9/2002 (LR) #

Yunnan/163/2002 #Aus-Bangkok/60/2002

Ohio/2/2002Brazil/2459/2002 (LR)Gaughwa/19/2002 (LR)

Aus-Sydney/200/2002Aus-Sydney/3/2002

NIID-Sendai/h1754/2001 (LR) #**NIPH-Oslo/668/2002

NIID-Akita/2/2002 #NIID-Sapporo/7/2002 (LR)

Hong Kong/1470/2002 (LR) #NIPH-Oslo/1870/2002

Tennessee/4/2002 (LR)Arizona/4/2002 (LR)

Chile/3162/2002 (LR) #New York/44/2002

NIID-Shizuoka/15/2001 #**NIMR-Lazio/1/2002

NIMR-Lyon/125/2002Peru/3132/2002 (LR)

NIMR-Barcelona/460/2002Colombia/3438/2002

Mexico/418/2001 (LR)Fujian/141/2001 #

Aus-Victoria/504/2000 #NIID-Shizuoka/480/2000 #

NIMR-Perm/3/2002Sichuan/379/99 #**

Yamanashi/166/98 #Beijing/184/93 #

R 69 GT 121 AR 136 KN 165 DT 182 AK 183 N

L 58 FN 126 D

H 40 Y

K 48 RT 168 N

N 126 D

Shanghai/361/2002 #

10 nucleotides

Page 29: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Thailand/163343/2002 (LR)

Aus-Brisbane/17/2002 #Iowa/3/2002 (LR) #

Idaho/4/2002 (LR)Aus-Auckland/14/2002

Aus-Brisbane/32/2002 (LR) #**Aus-Brisbane/28/2002 #

Aus-Perth/82/2002NIMR-Lisbon/190/2002

Louisiana/1/2002 (LR)NIMR-Madagascar/67860/2002 #**

Tianjin/130/2002Oman/16291/2001 (LR)

California/5/2002Taiwan/1519/2002 (LR)

Brazil/1730/2002 #Nevada/5/2002

New York/43/2002Texas/57/2002 (LR) **

Wisconsin/1/2003Missouri/12/2002

NIMR-Hong Kong/302/2002Hawaii/5/2002 (LR)Hong Kong/1351/2002 #Panama/486105/2002

Chile/13677/2002 #Mexico/963/2002 (LR)

Argentina/mc16/2002 (LR)Brazil/1733/2002 (LR) #Guatemala/20/2002 (LR)

New Hampshire/1/2002Beijing/243/97 #

Shandong/7/97 #**Guam/345/2002

NIID-Saitama/22/2002 #NIID-Sendai/h1023/2002 #NIID-Tokyo/127/2002 #NIID-Shiga/20/2002 #

Hong Kong/1115/2002 (LR) #Hong Kong/167/2002 #Hong Kong/1345/2002 #Hong Kong/1434/2002 #**

Wisconsin/7/2002Guangzhou/332/2002 (LR) #

Taiwan/1507/2002 (LR)Hong Kong/330/2001 #**

Hong Kong/335/2001 #NIID-Akita/27/2001 #

Taiwan/217/97

South Carolina/8/2002 (LR)I 121 T

H 116 RE 121 ND 164 E

5 nucleotides

Vaccine StrainEgg-Grown Isolate #Serology Antigen **Low Reactor (LR)

EVOLUTIONARY RELATIONSHIPS AMONG INFLUENZA B HA1 GENES (VICTORIA LINEAGE)

Page 30: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Restriction Analysis of Influenza B Isolates

U.S.A. North America

Europe Asia Cent/So America

Africa, Australia,

New Zealand

Total (%)

April 2002 - September 2002

B/Yamanashi/166/98/ B/Sichuan/379/99 lineage

3

8

6

17 (4%)

B/Harbin/07/94 lineage 2 14 5 21 (5%)

B/Hong Kong/330/01 lineage 1 14 15 (4%)

B/Oman/16296/2001 lineage 103 85 119 27 334 (87%)

Total 387

October 2003 - March 2003

B/Yamanashi/166/98/ B/Sichuan/379/99 lineage

1

1 (0.5%)

B/Harbin/07/94 lineage 1 6 7 (4%)

B/Hong Kong/330/01 lineage 2 46 48 (26.5%)

B/Oman/16296/2001 lineage 57 1 3 59 4 1 125 (69%) 181

Total 181

Total 424 6 44 486 231 33 1224

Preliminary Data 02/18/2003

Page 31: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Neuraminidase Inhibition Test of Influenza B viruses

STRAIN DESIGNATION FERRET ANTISERAA B C D Date

REFERENCE ANTIGENS Sic/379 Bris/32 SH/7 HK/330 collected

1 B/Sichuan/379/99 (Sic-Sic) 640 480 20 80 12/02/992 B/Brisbane/32/2002 (SH-Sic) 320 1280 40 320 07/02/023 B/Shandong/7/97(SH-Vic) 160 160 1280 2560 11/03/974 B/Hong Kong/330/02 (HK-Vic) 80 320 640 1280 04/09/01

TEST ANTIGENS

5 B/Texas/53/2002 (SH-Sic) 240 480 120 80 11/19/026 B/Philippines/198389/2002 (SH-Sic) 640 480 20 160 11/07/027 B/Guangzhou/332/2002 (HK-Vic) 80 160 320 640 08/29/02

Page 32: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Victoria/504/2000*Shizuoka/480/2000

Alaska/16/2000Shenzhen/804/2001#

Brazil/956/2001*#Hong Kong/692/2001*

nimr-Yamanashi/166/98Brazil/952/2001#

P42S, R69E

Niid-Shizuoka/15/2001*#E148G

Texas/22/20001*

Argentina/132/2001Argentina/69/2001

Wuhan/2/2001#Johannesburg/69/2001*#

Fujian/407/2001Wuhan/356/2001#

Sichuan/317/2001*#Sichuan/776/2001#

Osaka/18/2001Shenzhen/306/2001#

Harbin/7/94

D329N

P42Q, N219K, D392E

Hawaii/36/2001Hawaii/10/2001#

Hong Kong/28/2001Hong Kong/6/2001

Hong Kong/330/2001*Canada/464/2001

Hong Kong/22/2001Bangkok/34/99Bangkok/54/99

Shandong/7/97Yamagata/16/88

M50T, C54S, V60F, R436K

*Serology Antigen# Egg isolate

10 nucleotides

Vaccine Strain

Sichuan/379/99*#Johannesburg/5/99

EVOLUTIONARY RELATIONSHIPS AMONG INFLUENZA B NA GENES

Page 33: Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta,

Summary: Influenza B Viruses

• Influenza B viruses are predominating in the U.S. and much of Europe during the current season

• Influenza B viruses on the “Victoria lineage have predominated worldwide; B viruses on the Sichuan lineage were isolated infrequently

• Most recent influenza B viruses have NAs most closely related antigenically and genetically to that of the B/Sichuan ref. Virus

• The influenza B viruses have remained stable genetically and antigenically since last September