Announcement

Collapse
No announcement yet.

Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness, February 2014 (WHO, edited)

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

  • Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness, February 2014 (WHO, edited)

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


    Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness, February 2014

    The development of representative candidate influenza vaccine viruses, coordinated by the World Health Organization (WHO), remains an essential component of the overall global strategy for pandemic preparedness.


    Zoonotic influenza viruses continue to be identified and evolve both genetically and antigenically, leading to the need for update of candidate vaccine viruses for pandemic preparedness purposes. Evaluation of the genetic and antigenic characteristics of these viruses, their relationship to existing candidate vaccine viruses, and their potential risks to public health, justify the need to select and develop new candidate vaccine viruses.

    Selection and development of a candidate vaccine virus represents a first step only towards timely vaccine production and does not imply a recommendation for initiating manufacture. National authorities may consider the use of one or more of these candidate vaccine viruses for pilot lot vaccine production, clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.

    This document summarizes the genetic and antigenic characteristics of recent zoonotic influenza viruses from humans and related viruses circulating in animals and updates the availability of candidate vaccine viruses. 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(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. This summary provides updates on the characterization of A(H5N1) viruses and the current status of the development of influenza A(H5N1) candidate vaccine viruses.


    Influenza A(H5N1) activity from 24 September 2013 to 17 February 2014

    A(H5N1) viruses have been detected in birds in Africa and Asia. Human infections have been reported to the WHO by Cambodia, China, Indonesia, and Viet Nam, countries in which infections have been detected in birds (Table 1). An A(H5N1) virus was also isolated from an individual in Canada who had recently travelled to China.


    Table 1. Recent influenza A(H5N1) activity reported to international agencies

    [Reporting country, area or territory - Host/source - Genetic clade*]
    • Bangladesh
      • Poultry - 2.3.2.1a
    • Cambodia
      • Poultry - 1.1.2
      • Human (9)# - 1.1.2
    • Canada
      • Human (1) - 2.3.2.1c
    • China
      • Poultry/environmental - 2.3.2.1b, 2.3.2.1c, 2.3.4, 7.2
      • Human (1) - 2.3.4
    • Egypt
      • Poultry - 2.2.1
    • Indonesia
      • Poultry - 2.1.3.2a, 2.3.2.1c
      • Human (2) - 2.1.3.2a
    • Viet Nam
      • Poultry - 1.1.2, 2.3.2.1c
      • Human (2) - 1.1.2, 2.3.2.1c
    _____

    * based on available sequences

    # denotes number of human cases with illness onset dates falling within reporting period


    The nomenclature for phylogenetic relationships among the haemagglutinin (HA) genes of A(H5N1) viruses is defined in consultation with representatives of the WHO, the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE) and academic institutions. An updated nomenclature report has been published(2).

    Viruses circulating and characterized from 24 September 2013 to 17 February 2014 belonged to the following clades.

    Clade 1.1.2 viruses were detected in poultry and humans in Cambodia and Viet Nam. Genetic characterization of the HA genes showed that these viruses were closely related to viruses detected previously in these countries. While some of the recent avian viruses from Viet Nam had reduced reactivity to post-infection ferret antisera raised against A/Cambodia/W0526301/2012, for which a candidate vaccine virus is in development, the majority of recent clade 1.1.2 viruses reacted well.

    Clade 2.1.3.2a viruses continue to circulate in Indonesia. The HA gene sequence of a recent 2013 human virus was similar to that of A/Indonesia/NIHRD11771/2011 for which a candidate vaccine virus has been derived. No antigenic information for this virus is available.

    Clade 2.2.1 viruses were detected in poultry in Egypt although no human infections were identified during this period. As compared to the candidate vaccine viruses produced from A/Egypt/N03072/2010 and A/Egypt/2321-NAMRU3/2007, the HA proteins of recent clade 2.2.1 viruses have accumulated a number of amino acid substitutions. These viruses showed reduced reactivity to post-infection ferret antisera raised against the candidate vaccine viruses. Further virus characterization is underway.

    Clade 2.3.2.1a viruses were detected in birds in Bangladesh. The HA genes of these viruses were similar to those of viruses detected previously. The viruses reacted well with post-infection ferret antiserum raised against A/duck/Bangladesh/19097/2013 for which a candidate vaccine virus is in development.

    Clade 2.3.2.1b viruses were detected in environmental samples from China. Genetically and antigenically these viruses were similar to the viruses previously detected and reacted well to post-infection ferret antisera raised against available candidate vaccine viruses.

    Clade 2.3.2.1c viruses were detected in birds and/or environmental samples in China, Indonesia and Viet Nam and in humans in Canada and Viet Nam. The HA genes of these viruses were similar to those of viruses previously detected. Antigenic analysis showed that many of these viruses, including the human virus from Canada, reacted well with a post-infection ferret antiserum raised against A/duck/Viet Nam/NCVD-1584/2012 for which a candidate vaccine virus has been proposed.

    Clade 2.3.4 viruses were detected in environmental samples and a human in China. The HA genes of these viruses were similar to A/Anhui/1/2005. Further antigenic characterization of viruses from this clade is pending and will determine if additional candidate vaccine viruses are required.

    Clade 7.2 viruses were detected in environmental samples collected in China. Genetically and antigencially these viruses were distinct from the available candidate vaccine viruses (Figure 1, Table 2). As clade 7.2 viruses have continued to be detected, the development of a new candidate vaccine virus derived from an A/environment/Hubei/950/2013-like virus is proposed.

    (...)


    Table 2. Haemagglutination inhibition reactions of influenza A(H5N1) Clade 7.2 viruses

    [clade - Post-infection ferret antiserum NCVD-016]
    • REFERENCE ANTIGEN
      • A/chicken/Viet Nam/NCVD-016/2008 (RG12) - 7.1 – 160
    • TEST ANTIGEN
      • A/environment/Hubei/950/2013 - 7.2 - <20
      • A/environment/Guizhou/00320/2013 - 7.2 - <20
      • A/environment/Shaanxi/02011/2012 - 7.2 - <20
      • A/environment/Shaanxi/01/2011 - 7.2 - <20
      • A/environment/Shaanxi/04/2011 - 7.2 - <20

    Influenza A(H5N1) candidate vaccine viruses

    Based on the available antigenic, genetic and epidemiologic data, an A/environment/Hubei/950/2013-like (clade 7.2) candidate vaccine virus is proposed. The available and proposed candidate A(H5N1) vaccine viruses are listed in Table 3. National authorities may consider the use of one or more of these candidate A(H5N1) vaccine viruses for pilot lot vaccine production, clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.

    As the viruses continue to evolve, new A(H5N1) candidate vaccine viruses may be developed.


    Table 3. Status of influenza A(H5N1) candidate vaccine virus development

    [Candidate vaccine viruses - Clade - Institution* - 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) - 2.1.1 - SJCRH – Yes
    • A/Indonesia/5/2005 (CDC-RG2) - 2.1.3.2 - CDC – Yes
    • A/Indonesia/NIHRD11771/2011 (NIIDRG-9) - 2.1.3.2a - NIID – 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) - 2.3.2.1a - CDC – Yes
    • A/barn swallow/Hong Kong/D10-1161/2010 (SJ-003) - 2.3.2.1b - 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/Guizhou/1/2013-like - 2.3.4.2 - CDC/CCDC – Pending
    • A/duck/Bangladesh/19097/2013-like - 2.3.2.1a - SJCRH – Pending
    • A/duck/Viet Nam/NCVD-1584/2012-like - 2.3.2.1c - NIBSC – Pending
    • A/Cambodia/W0526301/2012-like - 1.1.2 - CDC – Pending
    • A/environment/Hubei/950/2013-like - 7.2 - CDC/CCDC – Pending
    _____

    * Institutions distributing the candidate vaccine viruses:
    • CDC - Centers for Disease Control and Prevention, United States of America
    • CDC/NIV - Centers for Disease Control and Prevention, United States of America/National Institute of Virology, India
    • CDC/CCDC - Centers for Disease Control and Prevention, United States of America/China Center for Disease Control and Prevention
    • FDA - Food and Drug Administration, United States of America
    • NIBSC - National Institute for Biological Standards and Control, a centre of the Medicines and Healthcare products Regulatory Agency (MHRA), United Kingdom of Great Britain and Northern Ireland
    • NIID - National Institute of Infectious Diseases, Japan
    • SJCRH - St Jude Children’s Research Hospital, United States of America

    Influenza A(H7N9)

    Influenza A(H7) viruses have been detected in poultry populations worldwide with the associated disease ranging from mild to severe. Human infections with avian influenza A(H7N9) viruses were first reported to WHO on 31 March 2013.


    Influenza A(H7N9) activity from 24 September 2013 to 17 February 2014

    During this period, 220 human cases of avian influenza A(H7N9) virus infection were reported to WHO, bringing the total number of cases to 355 including 112 (3) deaths. Human cases (and genetically related avian and/or environmental viruses) have been restricted to China except for a single case in Malaysia detected in a traveler from Guangdong Province, China.

    Comparison of avian influenza A(H7N9) viruses isolated from humans, poultry and environmental samples using haemagglutination inhibition assays shows that limited antigenic diversity exists among this group of viruses and they remain antigenically similar to the candidate vaccine viruses derived from A/Anhui/1/2013-like viruses (Figure 2, Table 4).

    All recent avian influenza A(H7N9) viruses that have been tested remain susceptible to the neuraminidase inhibitor class of antiviral drugs.


    Table 4. Haemagglutination inhibition reactions of influenza A(H7N9) viruses

    [Post-infection ferret antiserum - Anhui 1 - Shanghai 2]
    • REFERENCE ANTIGENS
      • A/Anhui/1/2013 - 160 – 640
      • A/Shanghai/2/2013 - 320 – 2560
    • TEST ANTIGENS
      • A/Hong Kong/5942/2013 - 80 – 1280
      • A/Shanghai/02619/2014 - 320 – 640
      • A/Guangdong/02620/2014 - 320 – 1280
      • A/Guizhou/01502/2014 - 320 – 1280
      • A/Guangdong/02125/2014 - 160 – 640
      • A/Fujian/1/2014 - 640 – 2560
      • A/Zhejiang/07807/2014 - 320 – 2560
      • A/ Zhejiang /07802/2014 - 640 – 2560
      • A/Hunan/07833/2014 - 160 – 1280
      • A/Hunan/08963/2014 - 320 – 1280
      • A/Guangxi/08970/2014 - 320 – 2560
      • A/Guangxi/08971/2014 - 320 – 2560
      • A/environment/Guangdong/25003/2013 - 160 – 640
      • A/environment/Zhejiang/07818/2014 - 320 – 1280
      • A/environment/Hunan/07836/2014 - 160 – 640

    Influenza A(H7N9) candidate vaccine viruses

    Based on the current epidemiologic and virologic data, no new A(H7N9) candidate vaccine viruses have been proposed. Available A(H7N9) candidate vaccine viruses are shown in Table 5. National authorities may consider the use of one or more of these candidate A(H7N9) vaccine viruses for pilot lot vaccine production, clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.

    As the viruses continue to evolve, new A(H7N9) candidate vaccine viruses may be developed.


    Table 5. Status of influenza A(H7N9) candidate vaccine virus development

    [Candidate vaccine virus - Type - Institution* - Available]
    • A/Anhui/1/2013 (H7N9) IDCDC-RG33A - Reverse Genetics - CDC – Yes
    • A/Anhui/1/2013 (H7N9) NIBRG-268 - Reverse Genetics - NIBSC – Yes
    • A/Anhui/1/2013 (H7N9) NIIDRG-10.1 - Reverse Genetics - NIID – Yes
    • A/Anhui/1/2013 (H7N9) SJ005 - Reverse Genetics - SJCRH – Yes
    • A/Shanghai/2/2013 (H7N9) NIBRG-267 - Reverse Genetics - NIBSC – Yes
    • A/Shanghai/2/2013 (H7N9) CBER-RG4A - Reverse Genetics - FDA – Yes
    • A/Shanghai/2/2013 (H7N9) IDCDC-RG32A - Reverse Genetics - CDC – Yes
    • A/Shanghai/2/2013 (H7N9) IDCDC-RG32A.3 - Reverse Genetics - CDC – Yes
    ______

    * Institutions distributing the candidate vaccine viruses:
    • CDC - Centers for Disease Control and Prevention, United States of America
    • FDA - Food and Drug Administration, United States of America
    • NIBSC - National Institute for Biological Standards and Control, a centre of the Medicines and Healthcare products Regulatory Agency (MHRA), United Kingdom of Great Britain and Northern Ireland
    • NIID - National Institute of Infectious Diseases, Japan
    • SJCRH - St Jude Children’s Research Hospital, United States of America

    Influenza A(H9N2)

    Influenza A(H9N2) viruses are enzootic in poultry populations in parts of Africa, Asia and the Middle East. The majority of viruses that have been sequenced belong to the G1, chicken/Beijing (Y280/G9), or Eurasian clades. 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 from 24 September 2013 to 17 February 2014

    Two human cases of A(H9N2) infection have been reported, one in China and the other in China Hong Kong Special Administrative Region (Hong Kong SAR) in this period. Both human viruses had HA genes belonging to the Y280/G9 genetic lineage. A(H9N2) viruses continue to be isolated from birds in many regions of the world. Recent Y280/G9 lineage viruses demonstrate increased genetic heterogeneity and some, including the human virus from Hong Kong SAR and closely related viruses, show reduced reactivity to a post-infection ferret antiserum to the A/chicken/Hong Kong/G9/1997 candidate vaccine virus (Figure 3, Table 6).

    (...)


    Table 6. Haemagglutination inhibition reactions of influenza A(H9N2) viruses

    [Lineage - Post-infection ferret antiserum: HK/1073 - HK/33982 - BA/994 - IBCDC-2]
    • REFERENCE ANTIGENS
      • A/Hong Kong/1073/1999 - G1 - 320 - 640 - 10 - <10
      • A/Hong Kong/33982/2009 - G1 - 320 - 2560 - 20 – 10
      • A/Bangladesh/994/2011 - G1 - 80 - 160 - 1280 – 80
      • A/chicken/Hong Kong/G9/1997 IBCDC-2 - G9/Y280 - 20 - 40 - 80 – 320
    • TEST ANTIGENS
      • A/swallow/Vietnam/NCVD-2449/2012 - G9/Y280 - 20 - 80 - 80 – 320
      • A/chicken/Vietnam/NCVD-1156/2011 - G9/Y280 - <10 - 20 - 20 – 20
      • A/Hong Kong/308/2014 - G9/Y280 - 40 - 80 - 40 – 20

    Influenza A(H9N2) candidate vaccine viruses

    Based on the current antigenic, genetic and epidemiologic data, an A/Hong Kong/308/2014-like candidate vaccine virus is proposed. The available A(H9N2) candidate vaccine viruses are listed in Table 7. National authorities may consider the use of one or more of these candidate A(H9N2) vaccine viruses for pilot lot vaccine production, clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.

    As the viruses continue to evolve, new A(H9N2) candidate vaccine viruses may be developed.


    Table 7. Status of influenza A(H9N2) candidate vaccine virus development

    [Candidate vaccine viruses - Type - Clade - Institution* - 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 - Y280/G9 - CDC – Yes
    • A/Hong Kong/33982/2009 (IDCDC-RG26) - Reverse genetics - G1 - CDC – Yes
    • A/Bangladesh/994/2011 (IDCDC-RG31) - Reverse genetics - G1 - CDC – Yes
    Candidate vaccine viruses in preparation
    • A/Hong Kong/308/2014-like - Reverse genetics - Y280/G9 - SJCRH – Pending
    __________

    * Institutions distributing the candidate vaccine viruses:
    • CDC - Centers for Disease Control and Prevention, United States of America
    • NIBSC - National Institute for Biological Standards and Control, a centre of the Medicines and Healthcare products Regulatory Agency (MHRA), United Kingdom of Great Britain and Northern Ireland
    • SJCRH - St Jude Children’s Research Hospital, United States of America

    Influenza A(H10N8)

    Three cases of human infection with avian influenza A(H10N8) viruses were reported from Jiangxi Province, China, with onset dates from December 2013 to February 2014. All of these individuals had severe disease and two have died. All had reported contact with poultry or contaminated environments. To date, genetic information from one virus isolate is available, which showed all genes to be of avian origin and the internal genes to be derived from A(H9N2) viruses currently circulating widely in poultry in China4. This virus is susceptible to the neuraminidase inhibitor class of antiviral drugs. Information on the prevalence and distribution of A(H10N8) viruses in poultry in the region is limited, thus the assessment of its impact on public health is difficult.

    At this time, the virus is being evaluated for its growth and antigenic properties and diagnostic reagents are being prepared. WHO is monitoring the situation closely.
    __________

    (1) http://www.who.int/influenza/vaccines/virus/en/

    (2) WHO/OIE/FAO H5N1 Evolution Working Group. Revised and updated nomenclature for highly pathogenic avian influenza A(H5N1) viruses. John Wiley & Sons Ltd. 2014 (http://onlinelibrary.wiley.com/doi/10.1111/irv.12230/full#irv12230 )

    (3) Communication from Chinese Centers for Disease Control and Prevention (CDC)

    (4) Chen H et al. Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection : a descriptive study. Lancet. 2014 ( http://dx.doi.org/10.1016/S0140-6736(14)60111-2 )


    -
    -------
Working...
X