19 Oct 2012

Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness, September 2012 (WER, October 19 2012, edited)

[Source: World Health Organization, full PDF document: (LINK). Edited.]

Weekly epidemiological record / Relevé épidémiologique hebdomadaire, 19 october 2012, 87th year / 19 octobre 2012, 87e année, No. 42, 2012, 87, 401–412 - http://www.who.int/wer

Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness, September 2012

 

The development of representative candidate influenza vaccine viruses, coordinated by WHO, remains an essential component of the overall global strategy for pandemic preparedness. Comparisons of the candidate vaccine viruses with respect to antigenicity and their relationship to newly emerging viruses are ongoing and will be reported periodically by WHO.

 

(1) Influenza A(H5N1)

Since their re-emergence in 2003, highly pathogenic avian influenza A(H5N1) viruses have become enzootic in some countries and continue to cause outbreaks in poultry as well as sporadic human infections. The A(H5N1) viruses have diversified both genetically and antigenically leading to the need for multiple candidate vaccine viruses for pandemic preparedness purposes. This summary provides updates on the characterization of A(H5N1) viruses isolated from birds and humans, and the current status of the development of candidate A(H5N1) vaccine viruses.

 

Influenza A(H5N1) activity: 23 February –18 September 2012

A(H5N1) viruses have been detected in birds in Africa, Asia and the Middle East, and from a cat in Israel. Human infections have been reported to WHO by Bangladesh, Cambodia, Hong Kong Special Administrative Region of China (Hong Kong SAR), Egypt, Indonesia and Viet Nam, countries in which infections have also been detected in birds (Table 1).

 

Antigenic and genetic characteristics of influenza A(H5N1) viruses

The nomenclature for phylogenetic relationships among the haemagglutinin (HA) genes of A(H5N1) viruses is defined in consultation with representatives of WHO, the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE) and academic institutions. The updated nomenclature report can be found on the WHO website.(1)

Viruses circulating and characterized from 23 February to 18 September 2012 belonged to the following clades.

Clade 1.1 viruses were detected in poultry and humans in Cambodia and Viet Nam. Genetic characterization of the HA genes showed that the human and poultry viruses were closely related to each other and to viruses detected previously in these countries. The recent avian viruses reacted well with post-infection ferret antisera raised against the clade 1 virus A/Viet Nam/1203/2004 from which candidate vaccine viruses have been developed.

Clade 2.1.3.2 viruses were detected in humans in Indonesia during this period. Genetic characterization of the HA genes of these viruses and recently circulating viruses from poultry showed that they were similar to previously reported clade 2.1.3.2 viruses but are divergent from A/Indonesia/5/2005, from which a candidate vaccine virus has been developed (Figure 1). Viruses isolated from humans during 2011 and 2012 showed reduced titres to post-infection ferret antiserum raised against the candidate vaccine virus developed from A/Indonesia/5/2005 (Table 2).

Clade 2.2.1 viruses were detected in poultry and humans in Egypt, and in poultry and a cat in Israel. Viruses detected during the period were genetically similar to those isolated previously from poultry and humans in the region. Three human viruses isolated in 2012 reacted well with post-infection ferret antiserum raised against A/Egypt/N03072/2010, a virus from which a candidate vaccine virus has been developed.

Clade 2.3.2.1 viruses were detected in wild birds in Hong Kong SAR, India and Nepal, and in poultry in Bangladesh, Bhutan, China, India, Nepal and Viet Nam. Human cases were reported in Bangladesh and Hong Kong SAR. Increased genetic heterogeneity in HA gene sequences was observed within recent viruses from this clade. Two genetic groups, A/Hubei/1/2010-like (Figure 2) and A/barn swallow/Hong Kong/D10-1161/2010-like (Figure 3), were previously identified.

A third group, A/Hong Kong/6841/2010-like (Figure 4), is spreading in southeast Asia. The human virus from Hong Kong SAR and the majority of recent clade 2.3.2.1 avian viruses in the A/barn swallow/Hong Kong/D10-1161/2010-like genetic group reacted well with post-infection ferret antiserum raised against the candidate vaccine virus developed from A/barn swallow/Hong Kong/D10-1161/2010.

The majority of recent avian viruses from the A/Hubei/1/2010-like genetic group reacted well with postinfection ferret antiserum raised against the candidate vaccine virus developed from A/Hubei/1/2010. No viruses were isolated from the human cases in Bangladesh.

Recent avian viruses from the A/Hong Kong/6841/2010-like genetic group reacted well with post-infection ferret antiserum raised against the candidate vaccine virus developed from the clade 2.3.2.1 virus A/common magpie/Hong Kong/5052/2007.

Clade 2.3.4.2 viruses were isolated from poultry in Myanmar. Genetically these viruses were similar to A/chicken/Bangladesh/11RS1984-30/2011, from which the development of a candidate vaccine virus has been proposed.

A Clade 7.2 virus was isolated from poultry in China. No antigenic data for this virus are yet available.

 

Influenza A(H5N1) candidate vaccine viruses

Based on the available antigenic, genetic and epidemiologic data, a new A/Indonesia/NIHRD11771/2011-like clade 2.1.3.2 candidate vaccine virus is proposed. The available and proposed candidate A(H5N1) vaccine viruses are listed in Table 3. On the basis of geographic spread, epidemiology and antigenic and genetic properties of the A(H5N1) viruses in particular locations, national authorities may consider the use of one or more of these candidate vaccine viruses for pilot lot vaccine production, for clinical trials and other pandemic preparedness purposes.

As the viruses continue to evolve, new A(H5N1) candidate vaccine viruses will be developed and announced as they become available. Institutions that wish to receive these candidate vaccine viruses should contact WHO at gisrs-whohq@who.int or the institutions listed in announcements published on the WHO website.(2)

 

(2) Influenza A(H9N2)

Influenza A(H9N2) viruses are enzootic in poultry populations in parts of Asia and the Middle East. The majority of viruses that have been sequenced belong either to the G1 clade or the chicken/Beijing (Y280/G9) clade. Since 1998, when the first human infection was detected, the isolation of A(H9N2) viruses from humans and swine has been reported infrequently. In all human cases the associated disease symptoms have been mild and there has been no evidence of human-to-human transmission.

 

Influenza A(H9N2) activity: 23 February–18 September 2012

No human cases of A(H9N2) infections have been reported in the period. A(H9N2) viruses continue to be isolated from birds in many regions of the world.

 

Influenza A(H9N2) candidate vaccine viruses

Based on the current antigenic, genetic and epidemiological data, no new A(H9N2) candidate vaccine viruses are proposed. The available A(H9N2) candidate vaccine viruses are listed in Table 4. Institutions that wish to receive candidate vaccine viruses should contact WHO at gisrs-whohq@who.int or the institutions listed in announcements published on the WHO website.(2)

 

(3) Influenza A(H3N2) variant (v)(3)

Influenza A(H3N2) viruses are endemic in swine populations in many regions of the world. Depending on geographic location, the genetic and antigenic characteristics of these viruses differ. Human infections with swine A(H3N2) viruses have been documented in Asia, Europe and North America.(4)

 

Influenza A(H3N2)v activity: 23 February–18 September 2012

In multiple states of the United States, 305 human infections of A(H3N2)v have been detected since July 2012. Limited human-to-human transmission has been detected.

 

Characteristics of A(H3N2)v viruses

Genetically, the A(H3N2)v viruses were similar to viruses that circulate in swine in the United States and also to the previously reported A(H3N2)v virus.(5) These viruses reacted well with post-infection ferret antisera raised against A/Minnesota/11/2010 and A/Indiana/10/2011 viruses, from which candidate vaccine viruses (NYMC X-203 and NYMC X-213, respectively) have been prepared. The A(H3N2)v viruses tested so far were susceptible to neuraminidase inhibitors and resistant to the adamantanes.

 

Influenza A(H3N2)v candidate vaccine viruses

Based on the current antigenic, genetic and epidemiologic data, no new A(H3N2)v candidate vaccine viruses are proposed. Available candidate vaccine viruses are shown in Table 5. Institutions that wish to receive candidate vaccine viruses should contact WHO at gisrswhohq@who.int or the institutions listed in announcements published on the WHO website.(2)

 

(4) Influenza A(H1N1)v and A(H1N2)v

Influenza A(H1N1) and A(H1N2) viruses circulate in swine populations in many regions of the world. Depending on geographic location, the genetic and antigenic characteristics of these viruses differ. Human infections with swine A(H1) viruses have been documented for many years.(6)

 

Influenza A(H1N1)v and A(H1N2)v activity: 23 February–18 September 2012

Human infections with A(H1N1)v (1 case) and A(H1N2)v (3 cases) viruses have been detected in the United States in the reporting period.

 

Characteristics of influenza A(H1N1)v and A(H1N2)v viruses

The A(H1N1)v virus, which is similar to viruses that circulate in swine in the United States, contains an HA gene genetically and antigenically related to the A(H1N1)pdm09 viruses. The A(H1N2)v viruses are also similar to viruses known to circulate in swine in the United States and have HA genes similar to A(H1N1) viruses that circulated in humans until 2007. The A(H1N1)v and A(H1N2)v viruses were susceptible to oseltamivir and zanamivir and resistant to the adamantanes.

 

Influenza A(H1N1)v and A(H1N2)v candidate vaccine viruses

Based on the risk assessment of the antigenic and genetic characteristics of the A(H1N1)v and A(H1N2)v viruses, candidate vaccine viruses are not proposed at this time.

 

(5) Influenza A(H7N3)

Influenza A(H7) viruses cause sporadic outbreaks in poultry populations worldwide. Occasionally, during outbreaks in poultry, human cases are documented in those with direct poultry exposure. These infections often cause conjunctivitis with occasional respiratory disease.(7, 8)

 

Influenza A(H7N3) activity: 23 February–18 September 2012

Two human cases of conjunctivitis due to A(H7N3) viruses were reported by Mexico during the period. Both individuals were occupationally exposed to poultry associated with the ongoing highly pathogenic A(H7N3) outbreak in birds in the region. Fever and respiratory illness were absent in both cases.

 

Characteristics of influenza A(H7N3) viruses

A(H7N3) viruses isolated from infected poultry and humans in Mexico were genetically closely related (Figure 5). These viruses reacted well with post-infection ferret antiserum raised against A/Canada/RV444/2004, a virus from which a candidate vaccine virus has been developed (Table 6). The one human virus tested for susceptibility to antiviral drugs was sensitive to oseltamivir, zanamivir and the adamantanes.

 

Influenza A(H7) candidate vaccine viruses

Based on the current antigenic, genetic and epidemiologic data, no new A(H7) candidate vaccine viruses are proposed. Available A(H7) ca ndidate vaccine viruses are shown in Table 7. Institutions that wish to receive candidate vaccine viruses should contact WHO at gisrswhohq@who.int or the institutions listed in announcements published on the WHO website.(2)

 

 

Table 1 Influenza A(H5N1) activity, 23 February–18 September 2012

[Country, area or territory – Genetic clade]

  • Bangladesh
    • Poultry  - 2.3.2.1
    • Human (3)a - 2.3.2.1 [3]b
  • Bhutan
    • Poultry –  2.3.2.1
  • Cambodia
    • Poultry - 1.1
    • Human (2)  - 1.1 [2]
  • China
    • Poultry 2.3.2.1/7.2
  • China, Hong Kong SAR
    • Wild birds - 2.3.2.1
    • Human (1) - 2.3.2.1 [1]
  • Egypt
    • Poultry - 2.2.1
    • Humans (5) –  2.2.1 [2]
  • India
    • Poultry  - 2.3.2.1
    • Wild birds –  2.3.2.1
  • Indonesia
    • Poultry  - Unknown
    • Humans (5) - 2.1.3.2 [1]
  • Israel
    • Poultry  - 2.2.1
    • Feline –  2.2.1
  • Myanmar
    • Poultry –  2.3.4.2
  • Nepal
    • Poultry  - 2.3.2.1
    • Wild birds –  2.3.2.1
  • Viet Nam
    • Poultry  - 1.1/2.3.2.1
    • Humans (1) - 1.1 [1]

(a) Numbers in parentheses denote number of reported cases during this period.

(b) Numbers in brackets denote the number of viruses for which genetic information is available.

 

Table 2 Antigenic properties of influenza A(H5N1) 2.1.3.2 viruses

[Reference antigens – Reference ferret antiserum: Clade - IND/5 – RG2 - NIHRD1177/111 - IND/6]

  • A/Indonesia/5/2005 - 2.1.3.2 – 640 – 640 – 160 – 160
  • A/Indonesia/5/2005(IBCDC-RG2) - 2.1.3.2 – 640 – 640 – 80 – 320
  • A/Indonesia/NIHRD11771/2011 - 2.1.3.2 – 320 – 80 – 1280 – 40
  • A/Indonesia/6/2005 - 2.1.3.3  - 1280 – 640 – 320 – 640

Test antigens

  • A/Indonesia/NIHRD11931/2011 - 2.1.3.2 – 80 – 40 – 640 – 10
  • A/Indonesia/NIHRD11949/2012 - 2.1.3.2 – 80 – 40 – 640 – 10
  • A/Indonesia/NIHRD12379/2012 - 2.1.3.2 – 80 – 40 – 640 – 10

Numbers in bold indicate homologous antiserum/antigen titres.

 

Table 3 Status of development of influenza A(H5N1) candidate vaccine viruses, September 2012

[Candidate vaccine viruses – Clade – Institution(a) Available]

  • A/Viet Nam/1203/2004(CDC-RG; SJRG-161052) – 1 - CDC and SJCRH – Yes
  • A/Viet Nam/1194/2004(NIBRG-14) – 1 – NIBSC – Yes
  • A/Cambodia/R0405050/2007(NIBRG-88) - 1.1 – NIBSC – Yes
  • A/duck/Hunan/795/2002(SJRG-166614) - 2.1 – SJCRH – Yes
  • A/Indonesia/5/2005(CDC-RG2) - 2.1.3.2 – CDC – Yes
  • A/bar-headed goose/Qinghai/1A/2005(SJRG-163222) - 2.2 – SJCRH  - Yes
  • A/chicken/India/NIV33487/2006(IBCDC-RG7) - 2.2 - CDC/NIV – Yes
  • A/whooper swan/Mongolia/244/2005(SJRG-163243) - 2.2 – SJCRH – Yes
  • A/Egypt/2321-NAMRU3/2007(IDCDC-RG11) - 2.2.1 – CDC – Yes
  • A/turkey/Turkey/1/2005(NIBRG-23) - 2.2.1 – NIBSC – Yes
  • A/Egypt/N03072/2010(IDCDC-RG29) – 2.2.1 – CDC – Yes
  • A/Egypt/3300-NAMRU3/2008(IDCDC-RG13) - 2.2.1.1 – CDC – Yes
  • A/common magpie/Hong Kong/5052/2007(SJRG-166615) - 2.3.2.1 – SJCRH – Yes
  • A/Hubei/1/2010(IDCDC-RG30) - 2.3.2.1 – CDC – Yes
  • A/barn swallow/Hong Kong/D10-1161/2010(SJ-003) - 2.3.2.1 – SJCRH – Yes
  • A/chicken/Hong Kong/AP156/2008(SJ-002) - 2.3.4 – SJCRH – Yes
  • A/Anhui/1/2005(IBCDC-RG6) - 2.3.4 – CDC – Yes
  • A/duck/Laos/3295/2006(CBER-RG1) - 2.3.4 – FDA – Yes
  • A/Japanese white eye/Hong Kong/1038/2006(SJRG-164281) - 2.3.4 – SJCRH – Yes
  • A/goose/Guiyang/337/2006(SJRG-165396) – 4 – SJCRH – Yes
  • A/chicken/Viet Nam/NCVD-016/2008(IDCDC-RG12) - 7.1 – CDC – Yes
  • A/chicken/Viet Nam/NCDV-03/2008(IDCDC-RG25A) - 7.1 – CDC – Yes

Candidate vaccine viruses in preparation

[Clade – Institution – Availability]

  • A/chicken/Bangladesh/11RS1984-30/2011-like - 2.3.4.2 – CDC – Pending
  • A/Indonesia/NIHRD11771/2011-like - 2.1.3.2 – NIID – Pending

(a) Institutions distributing the candidate vaccine viruses.

CDC, Centers for Disease Control and Prevention, United States; CDC/NIV, Centers for Disease Control and Prevention, United States/National Institute of Virology, India; FDA, Food and Drug Administration, United States; NIBSC, National Institute for Biological Standards and Control, Health Protection Agency, England; NIID- National Institute of Infectious Diseases, Japan; SJCRH,St Jude Children’s Research Hospital, United States.

 

Table 4 Status of development of influenza A(H9N2) candidate vaccine viruses, September 2012

[Candidate vaccine viruses – Type - Clade – Institution(a) – Available]

  • A/Hong Kong/1073/1999 - Wild type – G1 – NIBSC – Yes
  • A/chicken/Hong Kong/G9/1997(NIBRG-91) - Reverse genetics – Y280/G9 – NIBSC – Yes
  • A/chicken/Hong Kong/G9/1997(IBCDC-2) - Conventional reassortant –  Y280/G9 – CDC – Yes
  • A/Hong Kong/33982/2009(IDCDC-RG26) - Reverse genetics – G1 – CDC – Yes
  • A/Bangladesh/0994/2011(IDCDC-RG31) - Reverse genetics –  G1 – CDC – Yes

(a) Institutions distributing the candidate vaccine viruses.

CDC, Centers for Disease Control and Prevention, United States; NIBSC, National Institute for Biological Standards and Control, Health Protection Agency, England.

 

Table 5 Status of development of A(H3N2)v candidate vaccine viruses, September 2012

[Candidate vaccine viruses – Type – Institution(a) – Available]

  • A/Minnesota/11/2010(NYMC X-203) - Conventional reassortant – CDC – Yes
  • A/Indiana/10/2011(NYMC X-213) - Conventional reassortant –  CDC – Yes

(a) Institutions distributing the candidate vaccine viruses.

Centers for Disease Control and Prevention, United States.

 

Table 6 Antigenic properties of influenza A(H7) viruses

[Reference ferret antiserum: Reference antigens – Subtype - NY/107 - CN/RV444 - CN/RV504 - ck/AR/10]

  • A/New York/107/2003 – H7N2 – 1280 – 160 – 320 – 10
  • A/Canada/RV444/2004 – H7N3 – 80 – 80 – 160 – 10
  • A/Canada/RV504/2004 – H7N3 – 80 – 160 – 320 – 10
  • A/chicken/Arkansas/10/2008 – H7N3 – 80 – 80 – 320 – 80

Test antigens

  • A/turkey/Virginia/4529/2002 – H7N2 – 1280 – 160 – 320 – 160
  • A/goose/Nebraska/17097-4/2011 – H7N9 – 80 – 160 – 320 – 10
  • A/Mexico/InDRE7218/2012 – H7N3 – 80 – 160 – 320 – 10

Numbers in bold indicate homologous antiserum/antigen titres.

 

Table 7 Status of development of influenza A(H7) candidate vaccine viruses (September 2012)

[Candidate vaccine viruses – Type – Institution(a) -  Availability]

  • A/turkey/Virginia/4529/2002(H7N2)IBCDC-5 - Conventional reassortant – CDC – Yes
  • A/mallard/Netherlands/12/2000(H7N7)IBCDC-1 - Conventional reassortant – CDC – Yes
  • A/mallard/Netherlands/12/2000(H7N3)NIBRG-60 - Reverse genetics – NIBSC – Yes
  • A/mallard/Netherlands/12/200(H7N1)NIBRG-63 - Reverse genetics – NIBSC – Yes
  • A/Canada/RV444/2004(H7N3) - Reverse genetics – SJCRH – Yes
  • A/New York/107/2003(H7N2)NIBRG-109 - Reverse genetics – NIBSC – Yes

(a) Institutions distributing the candidate vaccine viruses.

CDC, Centers for Disease Control and Prevention, United States; NIBSC, National Institute for Biological Standards and Control, Health Protection Agency, England; SJCRH, St Jude Children’s Research Hospital, United States .

__________________________

(1) Updated unified nomenclature system for the highly pathogenic H5N1 avian influenza viruses. Geneva, World Health Organization, 2011 (http://www.who.int/influenza/gisrs_laboratory/h5n1_nomenclature/en/ , accessed October 2012).

(2) Candidate vaccine viruses and potency testing reagents for influenza A(H5N1). Available at http://www.who.int/influenza/vaccines/virus October 2012.

(3) Standardization of terminology for the variant A(H3N2) virus recently infecting humans. Available at http://www.who.int/influenza/gisrs_laboratory/terminology_ah3n2v/en/ , accessed October 2012.

(4) Myers KP et al. Cases of Swine Influenza in Humans: A Review of the Literature. Clinical Infectious Diseases, 2007, 44:1084.

(5) See No. 10, 2012, pp. 83–95.

(6) Shu B et al. Genetic analysis and antigenic characterization of swine origin influenza viruses isolated from humans in the United States, 1990–2010. Virology, 2012, 422:151.

(7) Tweed SA et al. Human illness from avian influenza H7N3, British Columbia. Emerging Infectious Diseases, 2004, 10:2196.

(8) de Jong MC et al. Intra- and interspecies transmission of H7N7 highly pathogenic avian influenza virus during the avian influenza epidemic in the Netherlands in 2003. Revue scientifique et technique de l’Office international des épizooties (OIE), 2009, 28 (1):333–340.

 

-

-----