information for the vaccine and related biological products advisory committee cber, fda information...

INFORMATION FOR THE VACCINE AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE

CBER, FDA

Information Regarding Seasonal Influenza VirusesFEBRUARY 27, 2013

Nancy J. Cox, Ph. D.Director, Influenza Division

Director, WHO COLLABORATING CENTER FOR SURVEILLANCE, EPIDEMIOLOGY AND CONTROL OF INFLUENZA

Influenza DivisionNational Center for Immunization and Respiratory Diseases

Coordinating Center for Infectious DiseasesCenters for Disease Control and Prevention

Atlanta, GA 30333

Global Influenza Surveillance and Response Network (GISRS)

Global Influenza Surveillance and Response Network (GISRS)

All year around surveillance conducted by GISRS– 6 WHOCCs, 140 NICs, 4 ERLs, H5 Reference Laboratories

18-20 Feb 2013 WHO Consultation: Data review and analysis; write recommendations

Co-Chaired by Dr. Nancy Cox, WHOCC CDC Atlanta and Dr. Masato Tashiro, WHOCC, NIID Tokyo

– 9 Advisers: Directors of WHOCCs and ERLS• Disclosure of potential conflicts of interest • 18 observers from NICs, H5 Reference Laboratories, WHOCCs, WHO

ERLs, academic partners and the veterinary sector

Influenza B – September 2012-January 2013maximum influenza activity

Percentage of influenza viruses by subtypes(From 2 September 2012 – 2 February 2013)Percentage of influenza viruses by subtypes(From 2 September 2012 – 2 February 2013)

A(H5), 6 human viruses

Data source: FluNet, (www.who.int/flunet), Global Influenza Surveillance and Response System (15 February 2013)

http://www.who.int/flunet

Type and Subtype

Oseltamivir Zanamivir

Tested (n)

Normal

Reduced

Highly Reduced

Tested (n)

Normal

Reduced

Highly Reduced

US viruses: 1218 1215 1b 2c 1217 1217 0 0

A(H1N1)pdm09 81 79 0 2 80 80 0 0

A(H3N2) 767 767 0 0 767 767 0 0

B 370 369 1 0 370 370 0 0

Non-US viruses: 153 153 0 0 153 153 0 0

A(H1N1)pdm09 73 73 0 0 73 73 0 0

A(H3N2) 14 14 0 0 14 14 0 0

B 66 66 0 0 66 66 0 0

a Viruses were tested in the fluorescent NA inhibition assay. Inhibition is based on fold difference in IC50 of a test virus compared to the median IC50 value for type/subtype. The WHO AVWG criteria: Type A viruses - Normal: <10-fold; Reduced: 10-100-fold; Highly reduced: >100-fold.Type B viruses - Normal: <5-fold; Reduced: 5-50-fold; Highly reduced: >50-fold.b Influenza B/Maryland/07/2012 virus, GISIAD acc.no for NA: EPI399661.c H275Y was detected in two A(H1N1)pdm09 viruses.

Susceptibility to Neuraminidase Inhibitors: Inhibition of Neuraminidase Activitya

Virus collection period: Oct 01, 2012 - Jan 21, 2013

A(H1N1)pdm09 Viruses

Sept 2012 – Jan 2013

A(H1N1)pdm09 Viruses

Sept 2012 – Jan 2013

Number of A(H1N1)pdm09 Viruses Detected by GISRS



)H1N1(pdm09 Viruses Characterized During the Past 3Years, September to January

)H1N1(pdm09 low reactors in HI assays by WHO CCs

WHO CC A/Cal/7/09 Low (≥ 8 fold)

CDC152 (95%) 8 (5%)

CNIC 120 (98%) 2 (2%)

NIID8 (99%) 1 (1%)

NIMR94 (98%) 2 (2%)

VIDRL 18 (100%) 0 (0%)

Total 392 (96.8%) 13 (3.2%)

REFERENCE FERRET ANTISERA5 6 7

EGG MDCK EGG MDCK HA SEQ. DATEREFERENCE ANTIGENS CA/7 FL/27 MD/13 BA/2021 BA/2021 WA/24 WA/24 CO/14 GROUP CHANGE COLL. PASS.

1 A/CALIFORNIA/7/2009* 1280 1280 1280 160 640 1280 1280 256004/09/0

9 E3

2 A/FLORIDA/27/2011 2560 2560 2560 320 640 2560 2560 2560 510/30/1

1 E4

3 A/MARYLAND/13/2012 1280 1280 1280 80 320 1280 1280 2560 604/01/1

2 M1/C2

4 A/BANGLADESH/2021/2012* 40 80 40 320 320 160 40 320 6 N156S07/21/1

2 E4

5 A/BANGLADESH/2021/2012 40 80 40 320 320 160 20 320 6 N156S07/21/1

2 C1/C4

6 A/WASHINGTON/24/2012* 1280 1280 1280 160 320 2560 1280 2560 706/17/1

2 E4

7 A/WASHINGTON/24/2012 1280 1280 1280 80 320 1280 1280 640 706/17/1

2 C3

8 A/COLORADO/14/2012 1280 1280 1280 80 320 2560 1280 1280 703/28/1

2 C1/C2

TEST ANTIGENS

9 A/FLORIDA/60/2012 1280 1280 1280 80 160 1280 1280 256012/18/1

2 C1

10 A/MINNESOTA/28/2012 1280 1280 1280 80 160 1280 1280 256012/09/1

2 C2

11 A/MINNESOTA/30/2012 1280 1280 1280 80 320 1280 1280 256012/23/1

2 C1

12 A/OHIO/106/2012 1280 1280 1280 80 640 1280 1280 256011/29/1

2 C2

13 A/MINNESOTA/29/2012 640 640 640 80 320 1280 1280 128012/08/1

2 C2

14 A/PENNSYLVANIA/30/2012 640 640 1280 40 320 1280 1280 2560 612/04/1

2 C2

15 A/WISCONSIN/49/2012 640 640 640 80 160 640 640 128011/11/1

2 C2

16 A/WYOMING/30/2012 640 640 1280 80 160 1280 640 128012/19/1

2 C2

17 A/WYOMING/31/2012@ 640 1280 640 80 320 1280 1280 2560 7H275Y/

NA12/26/1

2 C1

18 A/NEW JERSEY/11/2012 320 320 640 40 160 640 640 128012/08/1

2 C2

19 A/NORTH CAROLINA/29/2012 320 320 320 20 80 320 320 640 612/27/1

2 M1/C1

20 A/TEXAS/99/2012 320 320 640 20 160 640 640 1280 6 12/17/1

2 M1/C1

21 A/CHIANG RAI/312/2012* 1280 1280 2560 160 640 2560 2560 2560 610/02/1

2 C2/C2

22 A/INDIA/2181/2012 1280 640 1280 80 160 1280 1280 2560 612/21/1

2 C1

23 A/INDIA/2192/2012 1280 1280 1280 160 640 1280 1280 2560 612/22/1

2 E3

24 A/INDIA/2243/2012 1280 640 1280 80 160 1280 1280 256012/28/1

2 C1

25 A/BANGLADESH/0019/2012 640 640 640 80 320 640 640 128009/18/1

2 C2

26 A/INDIA/2055/2012 640 320 640 80 320 640 640 1280 612/03/1

2 E3

27 A/INDIA/2055/2012 640 640 640 40 320 640 640 1280 612/03/1

2 C1

28 A/INDIA/2080/2012 640 640 1280 80 320 1280 1280 1280 612/06/1

2 C1

29 A/INDIA/2192/2012* 640 1280 1280 80 320 1280 1280 2560 612/22/1

2 C1

30 A/INDIA/2205/2012 640 640 1280 80 320 640 640 2560 612/24/1

2 E3

31 A/INDIA/2227/2012 640 640 1280 40 160 640 640 1280 6 12/25/1

2 C1

32 A/BANGLADESH/5011/2012 160 160 320 40 160 320 320 320 709/26/1

2 C2

33 A/INDIA/2150/2012 160 160 160 80 320 320 160 320 6 12/17/1

2 C2Sequence in GISAID

* Serology antigen

@ Oseltamivir resistant

All but 2 viruses tested were well inhibited by ferret antisera raised against A/California/07/2009 and other recent reference viruses.

The 2 low reactors did not acquire changes at positions153-157.

HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA A(H1N1)pdm09 VIRUSES (01/23/13)

REFERENCE FERRET ANTISERA 5 6 7

X-179 HA SEQ. DATE

REFERENCE ANTIGENS CA/7 CA/7 FL/27 MD/13BA/

2021BA/

2021 WA/24 WA/24 CO/14 GROUPCHANG

E COLL. PASS.

1 A/CALIFORNIA/07/2009* 1280 160 640 1280 160 320 1280 1280 256004/09/0

9 E3

2A/CALIFORNIA/07/2009 X-179 320 320 80 160 160 640 320 80 320 G155E REASS. EX/E2

3 A/FLORIDA/27/2011 2560 160 1280 2560 320 640 2560 2560 2560 510/30/1

1 E4

4 A/MARYLAND/13/2012 1280 80 640 1280 80 160 1280 1280 2560 604/01/1

2 M1/C2

5 A/BANGLADESH/2021/2012* 160 80 160 160 640 640 320 160 320 607/21/1

2 E4

6 A/BANGLADESH/2021/2012 80 40 80 40 320 320 80 40 160 607/21/1

2 C1/C4

7 A/WASHINGTON/24/2012* 640 80 640 640 80 160 640 640 1280 706/17/1

2 E5

8 A/WASHINGTON/24/2012 1280 80 1280 1280 80 160 1280 1280 1280 706/17/1

2 C3

9 A/COLORADO/14/2012 640 80 640 640 40 80 640 640 1280 703/28/1

2 C1/C2TEST ANTIGENS

10 A/GEORGIA/01/2013 1280 80 1280 1280 80 160 1280 1280 256001/02/1

3 C1

11 A/MASSACHUSETTS/01/2013 1280 80 640 640 80 4160 1280 1280 1280 701/02/1

3 M1/C1

12 A/MASSACHUSETTS/02/2013 1280 80 640 640 80 160 1280 1280 1280 701/02/1

3 M1/C1

13 A/PENNSYLVANIA/34/2012 1280 80 1280 1280 80 160 1280 1280 128012/20/1

2 C2

14 A/TENNESSEE/09/2012 1280 80 1280 1280 80 160 1280 1280 1280 610/31/1

2 C3

15 A/TEXAS/106/2012 1280 80 640 640 80 160 1280 1280 1280 712/15/1

2 C1

16 A/WISCONSIN/01/2013 1280 80 640 640 80 160 1280 1280 128001/06/1

3 C1

17 A/WISCONSIN/02/2013 1280 80 1280 1280 80 160 1280 1280 128001/02/1

3 C1

18 A/HAWAII/42/2012 640 80 640 640 80 160 640 640 64012/02/1

2 M2/C1

19 A/HAWAII/43/2012 640 80 640 1280 80 160 640 1280 64012/04/1

2 M2/C1

20 A/NEW YORK/01/2013 640 80 640 640 80 160 640 640 1280 601/07/1

3 C2

21A/NEW BRUNSWICK/RV0041/2012 1280 80 640 1280 80 160 1280 1280 1280

12/02/12 X1/C1

22 A/ONTARIO/RV0013/2012 1280 80 640 640 80 160 640 1280 128012/12/1

2 X1/C1

23 A/ONTARIO/RV3144/2012 1280 80 640 640 80 160 1280 1280 64012/03/1

2 X1/C1

24 A/ONTARIO/RV3149/2012 1280 80 640 640 80 160 1280 1280 64012/12/1

2 X1/C1

25A/NEW BRUNSWICK/RV0040/2012 640 80 640 640 80 160 640 640 640

12/03/12 X1/C1

26 A/INDIA/2139/2012 2560 80 1280 1280 80 160 1280 1280 128012/17/1

2 C2

27 A/TANZANIA/2085/2012 2560 160 1280 2560 160 320 1280 1280 256012/10/1

2 C2

28 A/INDIA/2019/2012 1280 80 640 1280 40 160 640 1280 128011/26/1

2 C1

29 A/INDIA/2080/2012 1280 160 1280 1280 160 320 1280 1280 2560 612/06/1

2 E4

30 A/INDIA/2171/2012 1280 80 1280 1280 160 320 1280 1280 2560 612/19/1

2 E4

31 A/INDIA/2181/2012 1280 160 1280 1280 80 320 1280 1280 1280 612/21/1

2 E4

32 A/INDIA/2192/2012 1280 160 1280 1280 160 320 1280 1280 2560 612/22/1

2 E4

33 A/TANZANIA/2074/2012 1280 80 1280 1280 80 320 1280 1280 1280 712/05/1

2 C2

34 A/TANZANIA/2081/2012 1280 80 1280 1280 80 160 1280 1280 128012/03/1

2 C2

35 A/TANZANIA/332/2012 1280 80 1280 1280 80 160 1280 1280 128012/11/1

2 C1

36 A/TANZANIA/339/2012 1280 80 1280 1280 80 160 1280 1280 128012/18/1

2 C1

37 A/INDONESIA/PAL102/2012 160 160 160 160 320 640 320 160 320 6 G155E08/24/1

2 C2/C1Sequence in GISAID

* Proposed serology antigen

HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA A(H1N1)pdm09 VIRUSES (01/29/13)

Antigenic Cartography of A(H1N1)pdm09 Viruses

Sept 2012 to Feb 2013 – Gold, Aug 2011 to Aug 2012 – Blue, Earlier – Grey

A/California /07/2009

A/California/07/2009 Apr # F $NYMC X179A A/California/07/2009 # F

NYMC X181 A/California/07/2009 #nimr A/Dakar/20/2012 DecA/Cote DIvoire/1575/2013 Jan

A/Nigeria/7781/2012 OctA/Minnesota/16/2012 Oct

A/Minnesota/03/2011 Feb FA/Minnesota/03/2011 Feb # F

afrims A/Thailand/KPPH-00066/2012niid A/Laos/I650/2012 Aug @ *

namru2 A/Cambodia/FSS23932/2012 DecA/Chiang Rai/312/2012 Oct $

nimr A/Netherlands/507/2012 Aug @cnic A/Jilin-Chaoyang/SWL1709/2012 Dec

A/Bangladesh/2021/2012 Jul LR # F C$A/Bangladesh/2021/2012 Jul LR Fnimr A/Ukraine/3/2013 Jan

A/Florida/02/2013 JanA/Wisconsin/02/2013 Jan

A/India/2192/2012 Dec # FA/India/2192/2012 Dec F $

A/India/2150/2012 Dec LRA H1pdm09 HA Consensus 2012-13

nimr A/Norway/35/2013 Jannimr A/England/658/2012 Dec

A/New York/01/2013 JanA/Gansu-Ganzhou/33/2012 Nov #

hk A/Hong Kong/62/2013 JanA/Tanzania/340/2012 Dec #

A/Utah/01/2013 JanA/Cote DIvoire/1529/2012 Dec #

A/Oman/412/2012 Decusafsam A/NewYork/1428/2013 Jan

A/Georgia/01/2013 Jan #cnic A/Beijing/SWLChaoyang-P031/2013 Jan LR

usafsam A/Korea/1419/2013 JanA/Japan/1419/2013 Jan

A/Washington/24/2012 Jun @ # F $A/Washington/24/2012 Jun @ F

namru6 A/Peru/FPI03819/2012nhrc A/SouthCarolina/x88/2012

usafsam A/SouthCarolina/22/2012 OctA/Wyoming/31/2012 Dec @

afrims A/Nepal/NPBH-00402/2012afrims A/Bhutan/BTA-00098/2012

A/Tanzania/2085/2012 Dec #nimr A/Ghana/DILI-0902/2012 Oct

cnic A/Beijing-Huairou/SWL11348/2012 Decniid A/Yokohama/1/2013 Jan *

A/Massachusetts/02/2013 Janusafsam A/SouthDakota/1411/2013 JanA/California/09/2013 Jan

hk A/Hong Kong/9259/2012 DecA/Ohio/02/2013 Jan

Evolutionary Relationships Among Influenza A (H1N1)pdm09 Hemagglutinin (HA) Genes, 2012-13

02/22/2013 Current Northern Hemisphere

Vaccine Strain

LR- Low Reactor to A/California/07/2009 Egg

(≥ 8 fold)

F - CDC Reference Antigen$- CDC Serology Antigen

C$- Common Serology Antigen@ - Oseltamivir Resistant

# Egg Isolate* – only HA1 region

October 2012November 2012December 2012January 2013

7

5

8

66173

(62%)

789

(32%)

811

(4%)

Unk5

(2%)

HA Genetic Groups Since September

2012

S185T S451N

P83S S203T I321V E374K

A197T

S143G

K163I V520A

S84G

D97N

K283EE499K

H138RV249L

V234I

H51NI295V

R205K V249L I216V

A186T V272A N473D T474K V520A

N156S

N125S

K163QA256T

I116MR205K

S69T N260D V520A

K154K/E

Evolutionary Relationships Among Influenza A (H1N1)pdm09 Neuraminidase (NA) Genes, 2012-13

02/22/2013 Current Northern

Hemisphere Vaccine Strain

LR- Low Reactor to A/California/07/2009 Egg

(≥ 8 fold)

F - CDC Reference Antigen$- CDC Serology AntigenC$- Common Serology

Antigen@ - Oseltamivir Resistant

H275Y# Egg Isolate

HA Genetic Group Shown


niid A/Yokohama/1/2013 Jan A/Ohio/02/2013 Jan

A/California/09/2013 Jan A/Massachusetts/02/2013 Jan

cnic A/Beijing-Huairou/SWL11348/2012 Dec nimr A/Ghana/DILI-0902/2012 Oct

A/Tanzania/2085/2012 Dec # A/Georgia/01/2013 Jan #

A/Cote DIvoire/1529/2012 Dec # nimr A/England/658/2012 Dec A/New York/01/2013 Jan

nimr A/Norway/35/2013 Jan A/India/2150/2012 Dec LR A/Wisconsin/02/2013 Jan

A/Utah/01/2013 Jan A/Tanzania/340/2012 Dec #

A N1pdm09 NA Consensus 2012-13 A/Oman/412/2012 Dec A/India/2192/2012 Dec F $ A/India/2192/2012 Dec # F

A/Florida/02/2013 Jan A/Gansu-Ganzhou/33/2012 Nov #

A/Washington/24/2012 Jun @ # F $ A/Washington/24/2012 Jun @ F

A/Wyoming/31/2012 Dec @ A/Japan/1419/2013 Jan

cnic A/Beijing/SWLChaoyang-P031/2013 Jan LR A/Minnesota/03/2011 Feb # F A/Minnesota/03/2011 Feb F

A/Chiang Rai/312/2012 Oct $ niid A/Laos/I650/2012 Aug @

nimr A/Netherlands/507/2012 Aug @ cnic A/Jilin-Chaoyang/SWL1709/2012 Dec

A/Minnesota/16/2012 Oct nimr A/Ukraine/3/2013 Jan

A/Bangladesh/2021/2012 Jul LR # F C$ A/Bangladesh/2021/2012 Jul LR F

A/Nigeria/7781/2012 Oct A/Cote DIvoire/1575/2013 Jan nimr A/Dakar/20/2012 Dec

A/California/07/2009 Apr # F $ NYMC X179A A/California/07/2009 # F NYMC X181 A/California/07/2009 #

7

5

8

6

7

6

G41R N44S ADD GLY

L40V I106V

N200S

N248D

V241I N369K

D451G

N222D

N386SLOSS GLY

N386K LOSS GLY

V106I

F74V N385T

N44S ADD GLY

Summary - 1

A(H1N1)pdm09 viruses co-circulated in varying proportions along with A(H3N2) and B viruses.

Regional A(H1N1)pdm09 activity was reported by a few countries in Asia and Central America. An increase in activity was reported, with regional and widespread outbreaks in January in many countries in Europe. Widespread outbreaks were reported in Algeria in January.

Localized and sporadic influenza activity were reported in many other countries in northern Africa, Asia and North America.

Most A(H1N1)pdm09 viruses were antigenically similar to the recommended vaccine virus A/California/7/2009.

Most recent A(H1N1)pdm09 viruses belong to genetic Clades 6 and 7.

The majority of A(H1N1)pdm09 viruses were sensitive to oseltamivir. Of the small number of viruses that were resistant to oseltamivir, all had the H275Y mutation.

Summary - 2Summary - 2

A(H3N2) Viruses

Sept 2012 – Jan 2013

A(H3N2) Viruses

Sept 2012 – Jan 2013

Number of A(H3N2) Viruses Detected by GISRS



H3N2 Viruses Characterized During the Past 3 Years from September to January

H3N2 Viruses Characterized During the Past 3 Years from September to January

USA China Japan UK Australia

H3 low reactors in HI assays by WHO CCsH3 low reactors in HI assays by WHO CCs

WHO CC A/Vic/361/11 (MDCK)

Low (≥ 8 fold)

CDC 761 (99%) 5 (1%)

CNIC 829 (100%) 0 (0%)

NIID 88 (98%) 2 (2%)

NIMR 115 (95%) 6 (5%)

VIDRL 117 (100%) 0 (0%)

Total 1923 (97%) 13 (3%)

Influenza A(H3N2) Isolates Characterized by CDC

U.S.A. North America

Europe Asia Cent/So America

Africa, Australia,

New Zealand

Total (%)

September 2011 – February 2012

A/Perth/16/2009-like* 303 1 8 45 23 9 389 (37%)

A/Perth/16/2009-like** 322 8 56 18 21 425 (40%)

A/Perth/16/2009-like (low)*** 156 6 16 38 4 26 246 (23%) %

Total 1060

March 2012 – August 2012

A/Perth/16/2009-like* 237 1 11 5 36 7 297 (30%)

A/Perth/16/2009-like** 270 2 16 21 45 15 369 (37%)

A/Perth/16/2009-like (low)*** 171 1 33 28 22 7 262 (26%) %

A/Victoria/361/2011* 22 1 25 17 8 73 (7%)

A/Victoria/361/2011** 1 1 (<1%)

Total 1002

September 2012 – January 2013

A/Victoria/361/2011#* 694 8 22 10 8 742 (88%) %)

A/Victoria/361/2011** 85 3 5 93 (11%)

A/Victoria/361/2011 (low)*** 4 1 5 (<1%)

Total 840

Total 2264 19 93 244 176 106 2902 FOR H3 TEMP1

Dat

# Cell- propagated A/Victoria/361/2011 * < 4-fold low to vaccine strain Preliminary Data 02/14/13 ** = 4-fold low to vaccine strain *** ≥ 8-fold low to vaccine strain

REFERENCE FERRET ANTISERA

3C

EGG MDCK EGG MDCK HA SEQ DATE

REFERENCE ANTIGENS VIC/361 VIC/361 TX/50 TX/50 GROUP CHANGES COLL. PASS.

1 A/VICTORIA/361/2011 1280 320 320 320 3C H156Q, G186V,S219Y1

10/24/11 E3/E3

2 A/VICTORIA/361/2011 40 160 160 160 3C10/24/1

1 C2/C3

3 A/TEXAS/50/2012 640 1280 640 640 3CT128N, G186V, S198P,

S219F2

04/15/12 E5

4 A/TEXAS/50/2012 40 160 160 160 3C T128N, S198P2

04/15/12 M1/C2

5 A/TEXAS/50/2012 X-223 640 640 320 320 3C I226N3 REASS

6 A/TEXAS/50/2012 X-223A 640 640 320 320 3C I226N3 REASS

TEST ANTIGENS4

7 A/ARKANSAS/05/2012 80 640 320 320 3A12/19/1

2 C2

8 A/VIRGINIA/03/2013 80 320 320 320 3C T128A, R142G, N145S2

01/04/13 C2

9 A/NEW HAMPSHIRE/21/2012 40 160 160 160 3C T128A, R142G, N145S2

12/14/12 R1/C1

10 A/SOUTH CAROLINA/16/2012 80 160 160 160 511/07/1

2 M1/C2

11 A/KANSAS/16/2012 20 80 80 80 3C T128A, R142G, N145S2

12/12/12 C1

12 A/MASSACHUSETTS/15/2012 40 80 80 80 3C T128A, R142G, N145S2

12/18/12 C1

13 A/COTE D'IVOIRE/1331/2012 80 160 160 32011/07/1

2 X/C1

14 A/SAPPORO/125/2012 40 160 160 160 3C N145S3

11/01/12 C1/C1

15 A/HUBEI-HONGSHAN/1368/2012 80 160 160 160 3C N145S3

09/26/12 C4/C2

16 A/JIANGSU-XIUCHENG/1358/2012 80 160 320 160 3C T128A, R142G, N145S3

09/04/12 C3/C2

17 A/LAOS/717/2012 80 320 160 32009/17/1

2 C2/C1

18 A/LAOS/727/2012 80 160 160 160 09/17/1

2 C1/C1

HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA H3 VIRUSES (GUINEA PIG RED BLOOD CELLS) (01/24/13)

1 .Egg-propagated A/Victoria/361/2011 differs from the cell-propagated A/Victoria/361/2011 at the 3 positions indicated .

2 .Substitution in the HAs of the clade 3C viruses compared to cell-propagated A/Victoria/361/2011.3 .Substitution in the HAs of the A/Texas/50/2012 reassortants compared to egg-propagated A/Texas/50/2012.4 .All test viruses were cell-propagated.

Neutralization titer

Post infection ferret sera

Viruses A/Stockholm A/Athens A/Vic A/Vic

Collection Passage 18/11 112/12 361/11 361/11

Date History T/C F28/11 T/C F16/12 Egg F35/12 T/C F14/12

Genetic group group 3A group 3B group 3C group 3C

REFERENCE VIRUSES

A/Stockholm/18/2011 3A 3/28/2011 MDCK2/SIAT4 160 160 40 40

A/Athens/112/2012 3B 2/1/2012 SIAT4 160 320 40 160

A/Victoria/361/2011 3C 10/24/2011 E3/E2 80 160 5120 320

A/Victoria/361/2011 3C 10/24/2011 MDCK2/SIAT5 40 160 40 320

A/Texas/50/2012 3C 4/15/2012 E5/E1 320 640 320 640

TEST VIRUSES

A/England/565/2012 3B 5/31/2012 SIAT2/SIAT6 320 640 320 1280

A/England/587/2012 3C (128, 142) 10/31/2012 SIAT1/SIAT1 320 640 160 640


A/Austria/705367/2012 5 11/6/2012 SIAT1/SIAT1 160 640 160 640


A/Thuringen/33/12 3C 11/12/2012 C2/SIAT1 320 640 320 1280

A/Cairo/59/2012 3B 12/6/2012 C1/SIAT1 160 320 160 320

A/Norway/2496/2012 3C 12/10/2012 SIAT1 160 320 160 320

A/Austria/710638/2012 5 12/11/2012 SIAT1/SIAT1 160 320 160 640

A/Cairo/81/2013 3B 12/11/2012 C1/SIAT1 80 320 160 320

Antigenic Analysis of Influenza A(H3N2) Viruses - Plaque Reduction Neutralization (MDCK-SIAT)

Passage < 4-fold >8 fold total tested

n % n % n

VIC/361 C2/C3 446 99% 3 1% 449

VIC/361 E3/E3 85 19% 364 81% 449

VIC/361 IVR-165 EX/E2 0 0% 10 100% 10

TX/50 M1/C2 449 100% 0 0% 449

TX/50 E5 372 83% 77 17% 449

HI/22 C3 448 >99% 1 <1% 449

HI/22 E4 229 51% 210 47% 449

Summary of fold differences between reference viruses and test antigens in HI assays performed by CDC since

January 2013


A/Victoria/361/2011-cell

A/Victoria/361/2011-egg

Antigenic Cartography of A(H3N2) Viruses

A/Perth/16/2009

H3N2 Hemagglutinin changes compared toA/Victoria/361/2011-cell

Victoria/361/2011 cell grown$

Receptor binding site

Glycosylation site

Antigenic site B

Antigenic site D

Antigenic site C

Antigenic site E

Antigenic site A

G186V H156Q

S219Y

Victoria/361/2011 egg grown$ @

3C 3C

Texas/50/2012 cell grown^$

T128N

180° rotation

Q33R

N278K

S198P

¥N126

Texas/50/2012 egggrown$ @

S219F

G186V

H3N2 Hemagglutinin changes compared to A/Victoria/361/2011-cell

H3N2 Hemagglutinin changes compared toA/Victoria/361/2011- cell

G186V

I226S

A/Texas/50/2012 Apr # F $

A/Perth/16/2009 # FA/Jiangsu-Danyang/1647/2012 Oct #

A/Jiangsu-Donghai/57/2012 Sep #A/Puerto Rico/36/2012 Jun # FA/Virginia/16/2012 Dec #

A/Brisbane/299/2011 Aug # Fusafsam A/Florida/1378/2013 Jan

nimr A/Austria/710638/2012 DecA/Delaware/23/2012 Dec #

A/South Carolina/16/2012 Nov $A/Florida/01/2013 Jan

usafsam A/Texas/1406/2013 JanA/Tanzania/303/2012 Nov

A/Arkansas/05/2012 DecA/Alaska/24/2012 Oct #

A/Ohio/02/2012 Mar FA/Ohio/02/2012 Mar # FA/Ohio/02/2012 X-221 # F

namru2 A/Cambodia/FSS23444/2012 Novnimr A/Ukraine/551/2012 Dec

nimr A/Cairo/136/2012 DecA/Victoria/361/2011 Oct F $

A/Victoria/361/2011 IVR-165 # FA/Victoria/361/2011 Oct # F $

A/Hawaii/22/2012 Jul F $A/Hawaii/22/2012 Jul # F

A/Texas/50/2012 Apr F $

A/Texas/50/2012 X-223A # FA/Texas/50/2012 X-223 # F

A H3 HA Consensus 2012-13A/Seoul/3531/2012 Dec

A/Delaware/01/2013 Jan LRA/Delaware/15/2012 Nov F $

niid A/Yokohama/164/2012 Dec *A/Arizona/09/2012 Oct # F

A/California/04/2013 Janusafsam A/Washington/1531/2013 Jan

namru2 A/Cambodia/FSS22141/2013 NovA/North Carolina/02/2013 Jan

A/Ontario/RV2944/2012 Novcnic A/Heilongjiang-Xiangfang/11272/2012 Dec *

nimr A/Sachsen/2/2013 Janusafsam A/Florida/1324/2013 Janusafsam A/Guam/1490/2012 Dec

lrmc A/Italy/x178/2013 JanA/Illinois/01/2013 Jan

usafsam A/DistrictofColombia/1414/2013 Jannhrc A/Illinois/NHRC367623/2012 Dec *

A/Ohio/01/2013 JanA/South Dakota/12/2012 Oct #

usafsam A/Virginia/1373/2013 JanA/New York/03/2013 Jan

A/North Dakota/08/2012 Decnimr A/England/676/2012 Dec

A/Montana/01/2013 Janusafsam A/SouthDakota/1410/2013 Jan

usafsam A/Alabama/1197/2013 JanA/Colorado/27/2012 Dec

A/Oregon/15/2012 DecA/Nebraska/02/2013 Jan

cnic A/Beijing-Huairou/128/2013 Jan *A/Virginia/03/2013 Jan

nimr A/Athens GR/14/2013 JanA/Rhode Island/02/2013 Jan

A/Yamaguchi/30/2012 Oct LRusafsam A/NewYork/1365/2013 Jan

A/New York/39/2012 Oct #A/West Virginia/01/2013 Jan

lrmc A/Qatar/x119/2013 JanA/Beijing-Xicheng/12423/2012 Oct $

usafsam A/Georgia/1407/2013 JanA/Oklahoma/03/2013 JanA/North Carolina/01/2013 Jan

Evolutionary Relationships Among Influenza A (H3N2) Hemagglutinin (HA) Genes, 2012-13

02/22/2013

Current Northern Hemisphere Vaccine Strain

WHO Recommendation 2013-2014

LR- Low Reactor to A/Victoria/361/2011 cell

(≥ 8 fold)


Antigen# Egg Isolate

* – only HA1 region


3C.1

3B

6

3A

5

A/Perth/16/09-like

1

3C.2

3C.3

3C

K62EK144N

ADD GLYT212A

P162SI260M

R261Q

D53NY94HI230V E280A

S199A

K2EN8D LOSS

GLY

N144DLOSS GLY

N145S D487N

L3I D53N

N145SD487N

N144K LOSS GLY

V223I

A198SN312S

S45NADD GLY

T48I

Q33RN278K

N145S

T128ALOSS GLY

R142G

D489N

R33Q

H156QG186VS219Y

T128NLOSS GLY

A198P

G186V S219F

I226N

3A15

(02%)

3B13

(02%)

3C574

(80%)

584

(12%)

633

(05%)

12

(00%)


2012

Evolutionary Relationships Among Influenza A (H3N2) Neuraminidase (NA) Genes, 2012-13

02/22/2013



LR- Low Reactor to A/Victoria/361/2011 cell

(≥ 8 fold)


Antigen# Egg Isolate

HA Genetic Group Shown


A/New York/39/2012 Oct # A/West Virginia/01/2013 Jan

A/Rhode Island/02/2013 Jan A/Virginia/03/2013 Jan

A/North Carolina/01/2013 Jan A/Oklahoma/03/2013 Jan

nimr A/England/676/2012 Dec nimr A/Sachsen/2/2013 Jan

A/Ontario/RV2944/2012 Nov cnic A/Beijing-Huairou/128/2013 Jan

cnic A/Heilongjiang-Xiangfang/11272/2012 Dec A/North Dakota/08/2012 Dec

A/Ohio/01/2013 Jan A/Illinois/01/2013 Jan

A/Yamaguchi/30/2012 Oct LR A/Delaware/15/2012 Nov F $ niid A/Yokohama/164/2012 Dec

A N2 Consensus 2012-13 A/Delaware/01/2013 Jan LR

A/Seoul/3531/2012 Dec cnic A/Beijing-Xicheng/12423/2012 Oct $

A/Oregon/15/2012 Dec A/Montana/01/2013 Jan A/Nebraska/02/2013 Jan

A/Hawaii/22/2012 Jul # F A/Hawaii/22/2012 Jul F $

A/North Carolina/02/2013 Jan A/Texas/50/2012 Apr # F $

A/Texas/50/2012 X-223A # F A/Texas/50/2012 Apr F $

A/Texas/50/2012 X-223 # F A/Victoria/361/2011 IVR-165 # F A/Victoria/361/2011 Oct # F $ A/Victoria/361/2011 Oct F $

A/Ohio/02/2012 Mar # F A/Ohio/02/2012 Mar F $

nimr A/Cairo/136/2012 Dec nimr A/Ukraine/551/2012 Dec

A/South Carolina/22/2012 Nov A/Virginia/16/2012 Dec #

A/Puerto Rico/36/2012 Jun # F nimr A/Austria/710638/2012 Dec

A/Delaware/23/2012 Dec # A/Florida/01/2013 Jan

A/South Carolina/16/2012 Nov $ A/Brisbane/299/2011 Aug # F

A/Tanzania/303/2012 Nov A/Alaska/24/2012 Oct #

A/Arkansas/05/2012 Dec A/Jiangsu-Danyang/1647/2012 Oct # A/Jiangsu-Donghai/57/2012 Sep #

A/Perth/16/2009 # F

D93G

S315R T148T/I/K

)I/K LOSS GLY(D151/D/N/V/G/S/A

(N ADD GLY)

S367N ADD GLY

K369TI464L

D127N E258K I307M L338F N342D E381G N402D LOSS GLY

R430S

E221DT238A

V143M

L81PN402D

LOSS GLY

M24T

V143M

S416N H336N

E258KN329T LOSS GLY

R150H

D251VD304N

N43D

3B

3A

5/6

3C

A/Perth/16/09-like

1

Summary• Influenza A(H3N2) viruses caused widespread outbreaks in North

America and were the predominant circulating viruses globally. H3N2 viruses also caused regional or widespread activity in some Asian and European countries.

• The majority of recent A(H3N2) viruses tested were antigenically similar to the cell-propagated A/Victoria/361/2011 reference virus and egg and cell-propagated A/Texas/50/2012 viruses.

• Post-infection ferret antisera raised against the egg-propagated A/Victoria/361/2011 virus had HI and neutralization titers that were at least 8-fold lower compared to the homologous titer.

• The HA genes of most recent A(H3N2) viruses fell into phylogenetic clade 3C while a smaller proportion had HA genes that fell into other phylogenetic clades such as 3A, 3B, 5 and 6. These genetic clades were antigenically indistinguishable.

• All tested H3N2 viruses remained susceptible to neuraminidase inhibitors.

Influenza B Viruses

Sept 2012 – Jan 2013

Influenza B Viruses

Sept 2012 – Jan 2013

IntroductionIntroduction

In recent years both B/Victoria lineage and B/Yamagata lineage viruses have co-circulated.

During the 2012/13 Northern Hemisphere season, the proportion of B/Yamagata lineage viruses increased and this lineage predominated in many countries.

Influenza B viruses were 23% of totalInfluenza B viruses were 23% of total

A(H1N1)pdm09, 14306, 12%

A(H3), 47213, 39%

A(not subtyped), 30779, 26%



Influenza B viruses analyzed by WHO CCs September 2012 to January 2013

B/VictoriaB/Yamagata

Influenza B activityInfluenza B activity

Data source: FluNet, (www.who.int/flunet), Global Influenza Surveillance and Response System


Number of B Viruses Detected by GISRS



B viruses characterized during the past 3 NH seasons (Sept to Jan)

B viruses characterized during the past 3 NH seasons (Sept to Jan)

B low reactors in HI assays in WHO CCs

WHO CC Victoria (Bris/60/2008) Yamagata (Wisc/1/2010)

CDCLow Reactors

119 (80%)29 (20%)

312 (100%)0 (0%)

CNICLow Reactors

108 (94%)7 (6%)

25 (100%)0 (0%)

NIIDLow Reactors

19 (100%)0 (0%)

6 (100%)0 (0%)

NIMR*Low Reactors

26 (97%)1 (3%)

39 (58%)28 (42%)

(B/Stockholm/12/2011)*

VIDRLLow Reactors

163 (93%) 12 (7%)

15 (54%)13 (46%)

TotalLow Reactors

435 (90%) 49 (10%)

397 (91%) 41 (9%)

B/Victoria Lineage Viruses

REFERENCE FERRET ANTISERA Y2 Y3 V1

MDCK EGG MDCK EGG MDCK EGG EGG MDCK EGG MDCK HA DATE REFERENCE ANTIGENS EST/55669 MA/02 MA/02 WI/1 W1/1 TX/06 BRI/60 BRI/60 NV/03 NJ/1 GROUP COLL. PASS.

1 B/ESTONIA/55669/2011 640 320 320 160 320 160 20 5 5 5 Y-2 03/14/11C2C2/

C22 B/MASSACHUSETTS/02/2012 320 320 320 160 160 160 20 5 5 5 Y-2 03/13/12 E33 B/MASSACHUSETTS/02/2012 640 320 640 320 320 320 10 5 5 20 Y-2 03/13/12 M1/C2

4B/MASSACHUSETTS/02/2012 BX-51B 640 1280 320 160 320 160 20 5 5 5 REASS E3E7

5B/MASSACHUSETTS/02/2012 BX-51C 320 640 320 160 160 160 20 5 5 10 REASS E3E7

6 B/WISCONSIN/01/2010 80 80 40 160 160 80 5 5 5 5 Y-3 02/20/10 E47 B/WISCONSIN/01/2010 640 320 160 640 640 320 10 5 5 5 Y-3 02/20/10 C1/C28 B/TEXAS/06/2011 160 160 160 320 320 160 10 5 5 10 Y-3 02/16/11 E49 B/BRISBANE/60/2008* 5 5 5 5 5 5 1280 80 640 160 V-1A 08/04/08 E4/E4

10 B/BRISBANE/60/2008 5 5 5 5 5 5 640 160 640 320 V-1A 04/08/08CX,C4/

C111 B/NEVADA/03/2011 5 5 5 5 5 5 320 160 640 320 V-1A 02/02/11 E312 B/NEW JERSEY/1/2012 5 5 5 5 5 5 320 160 640 640 V-1A 04/26/12 C2

TEST ANTIGENS 13 B/WISCONSIN/15/2012 320 160 640 320 160 160 5 5 5 20 12/26/12 C114 B/ARKANSAS/03/2012 320 160 640 160 160 160 5 5 5 20 Y-2 12/26/12 C115 B/GEORGIA/01/2013 160 160 320 160 160 160 5 5 5 10 01/01/13 C116 B/GEORGIA/02/2013 320 160 320 160 160 160 5 5 5 10 Y-2 01/04/13 C117 B/NEW MEXICO/04/2012 320 160 640 160 160 160 5 5 5 20 Y-2 11/26/12 M1/C218 B/NEW YORK/01/2013 160 160 640 160 160 160 5 5 5 20 01/10/13 C119 B/OREGON/04/2012 160 160 320 160 160 160 5 5 5 10 Y-2 12/31/12 M1/C120 B/TEXAS/24/2012 160 160 640 160 160 160 5 5 5 10 Y-2 11/27/12 E3 21 B/WYOMING/01/2013 320 160 640 160 160 160 5 5 5 5 01/02/13 C122 B/TEXAS/38/2012 160 160 160 80 80 80 5 5 5 5 12/20/12 M1/C123 B/BANGLADESH/3009/2012 80 80 160 320 160 160 5 5 5 5 09/20/12 C224 B/INDIA/2178/2012 160 160 320 160 160 160 5 5 5 10 12/20/12 C125 B/INDIA/2239/2012 160 160 320 160 160 160 5 5 5 20 12/27/12 C126 B/INDIA/2242/2012 320 160 320 160 160 160 5 5 5 10 12/28/12 C127 B/TEXAS/37/2012 5 5 5 5 5 5 320 160 640 640 12/24/12 C128 B/UTAH/17/2012 5 5 5 5 5 5 320 160 640 640 V-1A 12/25/12 C129 B/NEBRASKA/13/2012 5 5 5 5 5 5 160 80 640 320 V-1A 12/30/12 C130 B/INDIA/2024/2012 5 5 5 5 5 5 160 80 320 320 V-1A 11/26/12 C1

HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA TYPE B VIRUSES (01/25/13)

B/Victoria Antigenic Cartography

Recent B/Victoria lineage viruses are antigenically similar to B/Brisbane/60/2008

B/Brisbane/60/2008-cell


B/Ohio/01/2005 Feb # LR FB/Hiroshima/09/2010 Sep # LR F

cnic A/Jiangsu-Runzhou/1697/2012 Nov # *niid B/Laos/I772/2012 Oct *

cnic A/Jiangxi-Xunyang/52/2012 Dec *afrims B/Thailand/KRCH-00010/2012

afrims B/Thailand/PMKA1934/2012B/Montana/06/2012 Oct LRB/Montana/05/2012 Oct # LR F

B/Brisbane/60/2008 Aug FB/Brisbane/60/2008 Aug # F $

B/Michigan/09/2011 Sep # Fnimr B/Denmark/23/2012 Novnamru6 B/Peru/IRPc00144/2012 *

B/Jiangsu-Hailing/1740/2012 Sep #cnic A/Jiangsu-Qingpu/11269/2012 Oct *

B/Nevada/03/2011 Feb # FB/Nevada/03/2011 Feb F

B/Uganda/2851/2012afrims B/Bhutan/BTF-00088/2012

B Victoria HA Consensus 2012-13usafsam B/Nebraska/1075/2012 Dec

usafsam B/Nebraska/908/2012 DecB/Nebraska/05/2012 Novcnic A/Jiangsu-Pingjiang/1494/2012 Dec *

namru6 B/Nicaragua/INI00520/2012 Nov *afrims B/Philippines/AFPA-00187/2012B/Louisiana/01/2012 Dec

B/Honduras/648/2012 Novcnic A/Jiangsu-Tianning/1676/2012 Dec # *

B/Tanzania/335/2012 Dec LRnimr B/Bayern/1/2013 Jan

usafsam B/Florida/1189/2012 Decusafsam B/Texas/770/2012 Dec

B/Peru/1634/2012 Octnamru6 B/Pampagrande/FPT01070/2012 Dec *namru6 B/Piura/FPP01690/2012 Dec *

B/Utah/17/2012 Decusafsam B/Nevada/847/2012 Dec

nimr B/Lyon/2760/2012 Decnimr B/Jordan/30014/2012 Dec

afrims B/Thailand/KPPH-00092/2012B/Bangkok/282/2012 Oct

B/Wisconsin/01/2013 Jan LRB/Wyoming/10/2012 Dec

B/India/2024/2012 Nov LRcnic A/Fujian-Yanping/2322/2012 Dec *

B/Bangladesh/3249/2012 Octaus B/Victoria/824/2012 Octusamruk B/Kenya/244/2012

afrims B/Philippines/AFPA-00149/2012B/Wisconsin/16/2012 Dec LR

B/Texas/02/2013 JanB/Virginia/05/2012 Dec LRB/New Jersey/02/2013 Jan LR

Evolutionary Relationships Among Influenza B Victoria Lineage Hemagglutinin (HA) Genes, 2012-13

02/22/2013

LR- Low Reactor to B/Brisbane/60/2008 Egg

≥)8 fold(

F - CDC Reference Antigen - $CDC Serology Antigen

#Egg Isolate - *HA1 region only

____ 165N


1A

1B

Intra-clade ReassortantsHA-1A/NA-3

Intra-clade ReassortantsHA-1B/NA-4

N75K N165K S172P

L58P

V87I N129S

N171D P58S

H122L

V15I

V146I

N218D

A169E

N129D

G184E

A154T

K209N

V1A133

(91%)

V1B12

(08%)

V41

(1%)


2012

Evolutionary Relationships Among Influenza B Victoria Lineage Neuraminidase (NA) Genes, 2012-13

02/22/2013

LR- Low Reactor to B/Brisbane/60/2008 Egg

≥)8 fold(


#Egg IsolateHA Genetic Group Shown


B/Texas/02/2013 Jan B/Wisconsin/16/2012 Dec LR

B/Virginia/05/2012 Dec LR B/New Jersey/02/2013 Jan LR

B/Honduras/648/2012 Nov B/Louisiana/01/2012 Dec insert L76

B/Nebraska/05/2012 Nov cnic A/Jiangsu-Pingjiang/1494/2012 Dec

cnic A/Jiangsu-Tianning/1676/2012 Dec # nimr B/Lyon/2760/2012 Dec B/Montana/05/2012 Oct # LR F B/Montana/06/2012 Oct LR B/Tanzania/335/2012 Dec LR

B/Wisconsin/01/2013 Jan LR B/Wyoming/10/2012 Dec

B/Peru/1634/2012 Oct B/Utah/17/2012 Dec

nimr B/Bayern/1/2013 Jan B Victoria NA Consensus 2012-13

nimr B/Jordan/30014/2012 Dec B/Bangkok/282/2012 Oct

aus B/Victoria/824/2012 Oct B/India/2024/2012 Nov LR

B/Bangladesh/3249/2012 Oct cnic A/Fujian-Yanping/2322/2012 Dec

B/Uganda/2851/2012 B/Nevada/03/2011 Feb # F B/Nevada/03/2011 Feb F

B/Brisbane/60/2008 Aug # F $ B/Brisbane/60/2008 Aug F

B/Jiangsu-Hailing/1740/2012 Sep # cnic A/Jiangsu-Qingpu/11269/2012 Oct

B/Hiroshima/09/2010 Sep # LR F cnic A/Jiangsu-Runzhou/1697/2012 Nov #

B/Ohio/01/2005 Feb # F B/Michigan/09/2011 Sep # F

nimr B/Denmark/23/2012 Nov cnic A/Jiangxi-Xunyang/52/2012 DecS41P P42S N125K V271I K272Q D320K D329E D340N D342G

D384N A395V K404E D463N A465T ADD GLY

T8M L73F A389T S397R

N340D

D329NI204V

N220KA358E

H61QK375M

S295R

D35G N59D R65S I348V A395T P51S

L73F N199D

V63M

K343E

L73F

L73F

N198SS345N

1A

1B

1BIntra-clade

ReassortantsHA-1A/NA-3

3Intra-clade

ReassortantsHA-1B/NA-4

4

B/Yamagata Lineage Viruses

Antigenic analysis of B/Yamagata viruses (1)Antigenic analysis of B/Yamagata viruses (1)

Viruses WISC MAL WELL WELL BRISEgg Cell Cell Egg Egg

REFERENCE VIRUSESB/WISCONSIN/1/2010 3 640 < 160 40 640B/MALAYSIA/412/2012 2 80 320 640 640 640B/WELLINGTON/3/20121 2 20 160 640 1280 640B/WELLINGTON/3/20121 2 20 160 640 640 640B/BRISBANE/36/2012 2 80 80 160 160 640

TEST VIRUSES*B/MALAYSIA/878/2012 3 320 < 80 20 320B/HYOGO/4002/2012 3 160 < 320 80 160B/VICTORIA/1028/2012 3 160 < 320 80 160B/DENMARK/31/2012 2 320 640 640 640 1280B/VICTORIA/834/2012 2 160 320 640 640 1280B/MASSACHUSETTS/02/2012 2 40 320 320 320 640B/YOKOHAMA/82/2012 2 40 320 320 320 640B/NEWCASTLE/1/2013 2 40 320 320 320 640

Homologous Titre2012-13 vaccine

1. < = <20; * Cell isolated and propagated

Genetic Clade

HI- titre1

Post-infection ferret antiserum

Antigenic analysis of B/Yamagata viruses (2)Antigenic analysis of B/Yamagata viruses (2)

Viruses B/Wis B/Estonia B/HK B/Mass B/MassEgg Cell Cell Egg Cell

REFERENCE VIRUSESB/Wisconsin/1/2010 3 640 40 160 640 40B/Estonia/55669/2011 2 80 640 1280 320 640B/Hong Kong/3577/2012 2 40 640 640 160 640B/Massachusetts/02/2012 2 160 80 320 640 40B/Massachusetts/02/2012 2 40 160 640 640 160

TEST VIRUSES*B/Paris/1443/2012 3 160 40 320 320 80B/Ghana/DILI-0859/2012 3 80 40 320 320 80B/Hyogo/4002/2012 3 80 40 160 320 80B/Paris/1448/2012 2 40 640 640 320 160B/New Mexico/04/2012 2 40 640 640 320 160B/Yokohama/82/2012 2 40 320 320 160 160

Homologous Titre2012-13 Vaccine

* Cell isolated and propagated

Genetic Clade

Haemagglutination Titre

Post-infection ferret sera

REFERENCE FERRET ANTISERA Y1 Y2 Y3

EGG MDCK EGG MDCK EGG MDCK HA DATE

FL/4EST/

55669 MA/02 MA/02 WI/1 W1/1 TX/06 TX/06 GROUP COLL. PASS.

1 B/FLORIDA/04/2006 5120 1280 1280 1280 320 640 320 640 Y-111/01/0

6 E3

2 B/ESTONIA/55669/2011 1280 640 320 320 160 320 160 320 Y-203/14/1

1C2C2/

C2

3 B/MASSACHUSETTS/02/2012 640 320 320 320 160 160 160 160 Y-203/13/1

2 E3

4 B/MASSACHUSETTS/02/2012 1280 640 320 640 320 320 320 320 Y-203/13/1

2 M1/C2

5B/MASSACHUSETTS/02/2012 BX-51B 2560 640 1280 320 160 320 160 320 REASS E3E7

6B/MASSACHUSETTS/02/2012 BX-51C 2560 320 640 320 160 160 160 160 REASS E3E7

7 B/WISCONSIN/01/2010 320 80 80 40 160 160 80 160 Y-302/20/1

0 E4

8 B/WISCONSIN/01/2010 1280 640 320 160 640 640 320 640 Y-302/20/1

0 C1/C2

9 B/TEXAS/06/2011 640 160 160 160 320 320 160 320 Y-302/16/1

1 E4

10 B/TEXAS/06/2011 320 160 160 160 320 320 320 640 Y-302/16/1

1 M1/C2TEST ANTIGENS

11 B/WISCONSIN/15/2012 320 320 160 640 320 160 160 32012/26/1

2 C1

12 B/ARKANSAS/03/2012 320 320 160 640 160 160 160 320 Y-212/26/1

2 C1

13 B/GEORGIA/01/2013 320 160 160 320 160 160 160 32001/01/1

3 C1

14 B/GEORGIA/02/2013 320 320 160 320 160 160 160 320 Y-201/04/1

3 C1

15 B/NEW MEXICO/04/2012 320 320 160 640 160 160 160 320 Y-211/26/1

2 M1/C2

16 B/NEW YORK/01/2013 320 160 160 640 160 160 160 32001/10/1

3 C1

17 B/OREGON/04/2012 320 160 160 320 160 160 160 320 Y-212/31/1

2 M1/C1

18 B/TEXAS/24/2012 320 160 160 640 160 160 160 160 Y-211/27/1

2 E3

19 B/WYOMING/01/2013 640 320 160 640 160 160 160 32001/02/1

3 C1

20 B/TEXAS/38/2012 320 160 160 160 80 80 80 160 12/20/1

2 M1/C1

21 B/BANGLADESH/3009/2012 160 80 80 160 320 160 160 32009/20/1

2 C2

22 B/INDIA/2178/2012 320 160 160 320 160 160 160 16012/20/1

2 C1

23 B/INDIA/2239/2012 320 160 160 320 160 160 160 32012/27/1

2 C1

24 B/INDIA/2242/2012 640 320 160 320 160 160 160 320 12/28/1

2 C1

HEMAGGLUTINATION INHIBITION REACTIONS OF INFLUENZA B/YAMAGATA-LINEAGE VIRUSES (01/25/13)

B/Yamagata Antigenic Cartography

Clade 2 and 3 viruses were antigenically distinguishable by many sera

B/Wisconsin/1/2010-egg


B/Massachusetts/2/2012-egg

B/Florida/04/2006 Nov # FB/Wisconsin/01/2010 Feb F $B/Wisconsin/01/2010 Feb # F $

B/Bangladesh/7005/2012 OctB/Hawaii/13/2012 Nov

cnic B/Heilongjiang-Jiguan/1409/2012 Dec *B/Nong Khai/322/2012 Oct

B/Hubei-Wujiagang/158/2009 Mar # FB/Vermont/07/2012 Decnimr B/Rheinland-Pfalz/4/2013 Janusafsam B/Nevada/845/2012 Dec

B/Texas/06/2011 Feb FB/Texas/06/2011 Feb # F

B/Cote DIvoire/1507/2012 Decnimr B/Ghana/DILI-0859/2012 Oct

B/Quebec/RV2958/2012 NovB/Dominican Republic/6986/2012 Dec

aus B/Brisbane/36/2012 JunB/Estonia/55669/2011 Mar F

afrims B/Thailand/KPPH-00148/2012B/Massachusetts/02/2012 Mar F $

aus B/Wellington/3/2012 JulB/Nevada/17/2012 Dec

B/Massachusetts/02/2012 BX-51C # FB/Massachusetts/02/2012 Mar # F $

B/Massachusetts/02/2012 BX-51B FB/Alabama/01/2013 Jan

B/Chanthaburi/318/2012 Octniid B/Yokohama/82/2012 Dec *

B/Texas/24/2012 Nov #usafsam A/Oklahoma/1557/2013 Janafrims B/Bhutan/BTG-00006/2012

usafsam B/Texas/1322/2013 Janusafsam B/Colorado/1468/2013 Janlrmc B/Germany/x170/2013 Jan

B/North Carolina/05/2012 DecB/New Mexico/04/2012 Nov $

nimr B/Lyon/2771/2012 DecB/India/2127/2012 Dec

B/Kansas/02/2012 DecB/Missouri/01/2013 Jan

usafsam B/Alaska/1351/2012 Decusafsam B/Illinois/704/2012 Dec

B/Oman/14/2013 Janusafsam B/SouthCarolina/1462/2013 Jan

B Yamagata HA Consensus 2012-13usafsam B/NewYork/1201/2013 Jan

B/India/2152/2012 Declrmc B/Belgium/x54/2012

B/Texas/01/2013 Janusafsam B/Florida/1376/2013 Jan

B/Ohio/01/2013 Janusafsam B/Maryland/583/2012 DecB/Georgia/02/2013 Jan

B/Georgia/04/2013 Jan

Evolutionary Relationships Among Influenza B Yamagata Lineage Hemagglutinin (HA) Genes, 2012-13

02/22/2013



LR- Low Reactor to B/Wisconsin/01/2010 Egg

≥)8 fold(


#Egg Isolate - *HA1 region only

October 2012November 2012December 2012January 2013February 2013

Y2

Y3

Y2217

(70%)

Y392

(30%)


2012

K88RE479D

R48KP108AT182AS230G

S150IN166YS230D

T182K

N203S

M252V

V29A L173Q

K299EE313K

T37A K299E E313K

N116K

T189A

N197D LOSS GLY

Evolutionary Relationships Among Influenza B Yamagata Lineage Neuraminidase (NA) Genes, 2012-13

02/22/2013



LR- Low Reactor to B/Wisconsin/01/2010 Egg

≥)8 fold(


#Egg IsolateHA Genetic Group Shown

October 2012November 2012December 2012January 2013February 2013

B/New Mexico/04/2012 Nov $ B/Ohio/01/2013 Jan

B/Texas/01/2013 Jan B/Georgia/02/2013 Jan

B/Georgia/04/2013 Jan B/Kansas/02/2012 Dec

B Yamagata NA Consensus 2012-13 B/India/2127/2012 Dec niid B/Yokohama/82/2012 Dec

nimr B/Lyon/2771/2012 Dec B/India/2152/2012 Dec

B/Chanthaburi/318/2012 Oct B/North Carolina/05/2012 Dec

B/Oman/14/2013 Jan B/Estonia/55669/2011 Mar F

aus B/Wellington/3/2012 Jul B/Nevada/17/2012 Dec

B/Massachusetts/02/2012 BX-51B F B/Massachusetts/02/2012 BX-51C F B/Massachusetts/02/2012 Mar # F $ B/Massachusetts/02/2012 Mar F $

aus B/Brisbane/36/2012 Jun B/Cote DIvoire/1507/2012 Dec nimr B/Ghana/DILI-0859/2012 Oct

B/Quebec/RV2958/2012 Nov B/Dominican Republic/6986/2012 Dec

B/Texas/06/2011 Feb # F B/Texas/06/2011 Feb F

B/Vermont/07/2012 Dec nimr B/Rheinland-Pfalz/4/2013 Jan

B/Hubei-Wujiagang/158/2009 Mar # F B/Wisconsin/01/2010 Feb # F $ B/Wisconsin/01/2010 Feb F $

B/Hawaii/13/2012 Nov B/Bangladesh/7005/2012 Oct

B/Nong Khai/322/2012 Oct cnic B/Heilongjiang-Jiguan/1409/2012 Dec

B/Florida/04/2006 Nov # F

Y2

Y3

D463NA465T

ADD GLY

Q42RA68TT125KK186RD340N

T106II248VS295R

A55T

R65H

L73PK343E

SummarySummary

B/Victoria and B/Yamagata lineage viruses co-circulated. The proportion of B/Yamagata viruses has increased in many

countries, while B/Victoria viruses predominated in some countries. B/Victoria lineage viruses

– Antigenically and genetically remain similar to the previously used vaccine virus, B/Brisbane/60/2008.

B/Yamagata lineage viruses– HA genes of the viruses were in clade 2 or 3.

– Clade 3 viruses were antigenically and genetically closely related to the 2012/13 NH vaccine virus, B/Wisconsin/1/2010.

– Some ferret antisera are able to detect antigenic differences between recent clade 2 and 3 viruses.

– Clade 2 viruses have circulated widely in recent months.

Summary of A(H1N1)pdm09 virusesSummary of A(H1N1)pdm09 viruses

A(H1N1)pdm09 viruses

• Continued to circulate at relatively low levels • Increase observed in some parts of Europe in January

• Viruses are antigenically similar to A/California/7/2009 vaccine virus

• HA genes are in clades 6 and 7 but these clades are antigentically indistinguishable.

Summary of influenza A(H3N2)Summary of influenza A(H3N2)

Predominant viruses globally and especially in Canada and the U.S. Some other countries in the Northern Hemisphere reported regional and widespread outbreaks.

Most recent viruses have HAs that:– Genetically fall into clade 3C; remainder fall into clades 3A, 3B, 5 and 6 – Antigenically indistinguishable– Antigenically similar to cell-propagated A/Victoria/361/2011, egg- and cell-

propagated A/Texas/50/2012 viruses– Showed at least 8-fold reduction in HI and NT using antisera against egg-

propagated A/Victoria/361/2011

Summary of influenza B (1)Summary of influenza B (1)

Influenza B viruses circulated and caused outbreaks in many countries.

Both B/Victoria/2/87 and B/Yamagata/16/88 lineages co-circulated.– B-Vic viruses prevalent in some countries (e.g., China)– B-Yam viruses continued to increase in proportion and becoming

dominant in many countries

The majority of recent B/Victoria/2/87 lineage viruses were antigenically and genetically closely related to B/Brisbane/60/2008.

Most recent B/Yamagata/16/88 lineage viruses– HA genes fall into clades 2 or 3, with the proportion of clade 2

viruses increasing significantly in Europe and North America– Many clade 2 vs. clade 3 viruses are antigenically distinguishable in

HI tests especially in laboratories in Melbourne and London

PublicationsPublications

Vaccine composition recommendation report and summary report on H5/H9 vaccine viruses:

– WHO GlSRS website:• http://www.who.int/influenza/gisrs_laboratory/en/• http://www.who.int/influenza/vaccines/virus/en/

– WHO Weekly Epidemiological Record:• http://www.who.int/wer/en/

Candidate vaccine viruses and reagents– http://www.who.int/influenza/vaccines/virus/en/

WHO Global Influenza Surveillance and Response System (GISRS):• [email protected]

http://www.who.int/csr/disease/influenza/vaccinerecommendations/en/index.html

http://www.who.int/csr/disease/influenza/vaccinerecommendations/en/index.html

http://www.who.int/wer/en/

http://www.who.int/influenza/vaccines/virus/en/

mailto:[email protected]

AcknowledgementsAcknowledgementsWHO Collaborating Centers in Beijing, London, Melbourne

and Tokyo for seasonal influenza data

National Influenza Centers (over 20 submitted written reports in addition to data provided through FluNet)

Essential Regulatory Laboratories for human serology data

Many staff from CDC’s Influenza Division, including Alexander (Sasha) Klimov, Xiyan Xu, Rebecca Garten, Julie Villanueva, Angie Foust, Wendy Sessions, Elizabeth Blanchard, Thomas Rowe, Jan Mabry, Jackie Katz, Vic Vegilla and many others

information for the vaccine and related biological products advisory committee cber, fda information...

Documents

seasonal influenza viruses

global influenza surveillance

reduced us viruses

type b viruses normal

number of ah1n1pdm09

influenza division director

nonus viruses

human viruses data source