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Recommended composition of influenza virus vaccines for use in the 2014 southern hemisphere influenza season, September 2013 (WHO, October 11 2013)

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  • Recommended composition of influenza virus vaccines for use in the 2014 southern hemisphere influenza season, September 2013 (WHO, October 11 2013)

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


    Weekly epidemiological record / Relevé épidémiologique hebdomadaire, 11 october 2013, 88th year / 11 octobre 2013, 88e année, No. 41, 2013, 88, 437–448, http://www.who.int/wer
    ____

    Recommended composition of influenza virus vaccines for use in the 2014 southern hemisphere influenza season, September 2013


    WHO convenes technical consultations(1) in February and September each year to recommend viruses for inclusion in influenza vaccines(2) for the northern and southern hemispheres, respectively.

    This recommendation relates to the influenza vaccines for the forthcoming influenza season in the southern hemisphere (2014). A recommendation will be made in February 2014 relating to vaccines that will be used for the influenza season in the northern hemisphere (2014–
    2015). For countries in equatorial regions, epidemiological considerations influence which recommendation (February or September) individual national and regional authorities consider appropriate.


    Seasonal influenza activity, February – September 2013

    Between February and September 2013, influenza activity was reported in Africa, the Americas, Asia, Europe and Oceania. Activity varied from low or moderate to high due to the circulation of influenza A(H1N1)pdm09, A(H3N2) and B viruses.

    In the northern hemisphere, influenza activity was moderate to high from February to April and started to decline from April onwards. For the southern hemisphere in general, activity increased in May and was declining in September. In tropical areas, activity was variable throughout the period.

    Influenza A(H1N1)pdm09 activity was variable in Africa, the Americas, Asia, Europe and Oceania. Regional and widespread outbreaks occurred in Europe between February and March and activity decreased after April. In Africa, widespread outbreaks occurred in Algeria and Tunisia in February and March. Regional and widespread outbreaks occurred from June until August in Madagascar and South Africa. A(H1N1)pdm09 predominated in Argentina, Brazil, and Chile from May through August. Regional to widespread outbreaks were reported in Australia in July and August. Sporadic to local activity was reported in New Zealand from May through August.

    In general, sporadic to local A(H1N1)pdm09 activity was reported in Asia and North America.

    Influenza A(H3N2) activity was variable in Africa, the Americas, Asia, Europe and Oceania. In Africa, sporadic activity was reported between February and August. In the Americas, sporadic to local activity was reported in Canada and Mexico in February and March, and local to regional activity was reported in the United States of America (USA) during the same period. Local to regional activity was reported in El Salvador from February through August and in Argentina and Panama from May through August. In Asia, regional to widespread outbreaks were reported in Japan in February and March. Activity was local in China and remained low in the rest of the region during this period. In Europe, from February to April many countries reported sporadic activity, although regional and widespread outbreaks reported in some countries including Croatia, Czech Republic, Germany, Hungary, Ireland, Netherlands, Russian Federation and Ukraine. In Oceania, sporadic activity occurred from February until June and increased in July with regional outbreaks reported in Australia.

    Widespread and regional outbreaks associated with influenza B viruses were reported in Europe and parts of Africa, the Americas, Asia and Oceania. In northern Africa, regional and widespread outbreaks were reported in Algeria and Tunisia in February and March. In southern Africa, local activity was reported in Madagascar from April until July. In the Americas, regional outbreaks were reported in the USA during February through April, and sporadic to local activity was reported in Canada and Mexico during the same time period. Activity was generally low in South America except Brazil where regional outbreaks were reported in May through August. In Asia, regional outbreaks were reported in Japan in March through June. Local to regional activity was reported in Hong Kong Special Administrative Region of China, in March and April.

    Regional to widespread outbreaks were reported in the majority of countries in Europe in February, and activity remained high through April. In Oceania, influenza B activity was sporadic in February through June and increased to regional activity in July and August. The extent and type of seasonal influenza activity worldwide are summarized in Table 1.


    Zoonotic influenza infections

    From 19 February to 23 September 2013, 16 confirmed human cases of A(H5N1) infection, 6 of which were fatal, were detected in Cambodia, Egypt, Indonesia and Viet Nam where highly pathogenic avian influenza A(H5N1) is present in poultry. Since December 2003, a total of 637 cases with 378 deaths have been confirmed in 15 countries.(3) To date there has been no evidence of sustained human-to-human transmission.

    Between February and 23 September 2013, 135 cases of A(H7N9) infection, including 44 deaths, were reported in China(4) with no evidence of sustained human-tohuman transmission.

    Eighteen cases of A(H3N2) variant (v) infection were detected in the USA from 21 June to 9 September 2013(5) with a total of 339 confirmed cases and one death since August 2011.

    The following zoonotic infections were also reported during this period: 2 human non-fatal cases of influenza A(H1N1)v in the USA; 3 cases of A(H7N7) conjunctivitis in Italy; 1 non-fatal case of A(H6N1) in Taiwan, China. No cases of A(H1N2)v, A(H7N3) or A(H9N2) infection were reported.


    Antigenic and genetic characteristics of recent seasonal influenza viruses

    Influenza A(H1N1)pdm09 viruses

    Between February and September 2013, all seasonal influenza A(H1N1) viruses detected worldwide were A(H1N1)pdm09. Haemagglutination inhibition (HI) tests using post-infection ferret antisera indicated that the majority of A(H1N1)pdm09 viruses remained antigenically homogeneous and closely related to the vaccine virus A/California/7/2009. Sequence analysis of the HA genes of A(H1N1)pdm09 viruses indicated that the viruses fell into several genetic clades which were antigenically indistinguishable. Recently circulating viruses belonged to clade 6 or 7, defined by S185T and S451N substitutions in the HA, with the great majority falling into clade 6, distinguished by the additional substitution D97N. A small proportion of viruses showed reductions in reactivity in HI assays with ferret antisera raised against A/California/7/2009-like reference viruses; most of these carried amino acid substitutions in the region corresponding to positions 153–157 of HA, often associated with propagation in cells, consistent with results obtained since May 2009.


    Influenza A(H3N2) viruses

    Antigenic characteristics of A(H3N2) viruses collected from February to August 2013 were assessed with panels of post-infection ferret antisera in HI and virus neutralization assays. The majority of recent A(H3N2) viruses were well inhibited by ferret antisera raised against cell-propagated reference viruses such as A/Victoria/361/2011 and A/Texas/50/2012. Post-infection ferret antisera raised against egg-propagated A/Texas/50/2012 inhibited many recent viruses, while ferret antisera raised against egg-propagated A/Victoria/361/2011 poorly inhibited most of the recent viruses. The HA genes of most recent A(H3N2) viruses fell into phylogenetic clade 3C, with small numbers in phylogenetic clades 3A, 3B, 5 and 6. Viruses in these genetic clades, including those clade 3C viruses with amino acid substitutions T128A, R142G and N145S, were antigenically indistinguishable in HI and neutralization assays.


    Influenza B viruses

    Influenza B viruses of the B/Victoria/2/87 and the B/Yamagata/16/88 lineages co-circulated. Viruses of the B/Yamagata/16/88 lineage were prevalent in all countries reporting influenza B infections. The HA genes of B/Yamagata/16/88 lineage viruses fell within genetic clades 2 or 3, with the majority in clade 2. Viruses with HA genes in these clades could be distinguished antigenically in HI tests by some post-infection ferret antisera. Post-infection antisera raised against the egg-propagated vaccine virus B/Massachusetts/2/2012 (a clade 2 virus) recognised the majority of recent viruses. Similarly, antisera raised against cell-propagated viruses from clade 2 also recognised the vast majority of test viruses.

    The HA gene sequences of most B/Victoria/2/87 lineage viruses belonged to the B/Brisbane/60/2008 genetic clade subgroup 1A and, in HI tests with postinfection ferret antisera, the majority of viruses were antigenically closely related to the vaccine virus, B/Brisbane/60/2008, and viruses closely related to B/Brisbane/60/2008 that were propagated in cells.


    Resistance to influenza antiviral drugs

    Neuraminidase inhibitors

    The majority of A(H1N1)pdm09 viruses tested were sensitive to oseltamivir and all were sensitive to zanamivir. Of the small number of A(H1N1)pdm09 viruses detected with highly reduced inhibition (HRI)(6) by oseltamivir, some were linked to the use of this drug for treatment; where tested these viruses also showed HRI by peramivir. In all instances, HRI was due to a histidine to tyrosine substitution at amino acid 275 (H275Y) in the neuraminidase. The great majority of A(H3N2) and B viruses tested were sensitive to oseltamivir, peramivir and zanamivir. The exceptions were: 3 A(H3N2) viruses which showed HRI by oseltamivir and carried the E119V substitution in the neuraminidase; 2 B/Victoria lineage viruses which showed HRI by peramivir and carried the H273Y substitution in the neuraminidase; and a small number of B/Victoria lineage viruses which showed reduced inhibition either by oseltamivir or by both oseltamivir and peramivir. A smaller number of viruses were also tested for susceptibility to laninamivir and all were sensitive.


    M2 inhibitors

    M gene sequencing of A(H1N1)pdm09 and A(H3N2) viruses revealed that all those analysed had the serine to asparagine substitution at amino acid 31 (S31N) of the M2 protein which is known to confer resistance to the M2 inhibitors, amantadine and rimantadine.


    Human serology studies with inactivated influenza virus vaccines

    HI assays were used to measure the presence of antibodies to recent virus isolates in panels of sera from children, adults and older adults who had received seasonal trivalent inactivated vaccines. For A(H3N2) viruses, virus neutralization assays were used for a subset of sera. One panel of sera from adults and older adults was obtained from recipients of the vaccine for the northern hemisphere 2013–2014 season (A/California/7/2009 (H1N1)pdm09-like, cell-propagated A/Victoria/361/2011 (H3N2)-like and B/Massachusetts/2/2010-like viruses); 3 panels of sera from adults and older adults as well as one panel from children were from trials of vaccine with the composition recommended for the southern hemisphere 2013 season (A/California/7/2009 (H1N1)pdm09-like, A/Victoria/361/2011 (H3N2)-like and B/Wisconsin/1/2010-like viruses).

    Vaccines containing A/California/7/2009-like antigens elicited anti-HA antibodies of similar geometric mean HI titres to the vaccine virus and the majority of representative recent A(H1N1)pdm09 viruses.

    Vaccines containing A/Texas/50/2012 (a virus antigenically like cell-propagated A/Victoria/361/2011) antigens elicited antibodies of similar geometric mean HI titres to the cell-propagated vaccine virus and the majority of representative recent A(H3N2) viruses. When compared with the titre to egg-propagated A/Texas/50/2012, titres against cell-propagated representative recent viruses were reduced (average reductions for cellpropagated A(H3N2) viruses compared to egg-propagated A/Texas/50/2012: adults, 81%; older adults, 79%; average reductions for egg-propagated A(H3N2) viruses compared to egg-propagated A/Texas/50/2012: adults, 31%; older adults, 27%; average reductions for cell-propagated A(H3N2) viruses compared to cell-propagated A/Texas/50/2012: adults, 31%; older adults, 28%).

    Vaccines containing influenza B/Massachusetts/2/2012-like antigens elicited anti-HA antibodies of similar geometric mean HI titres to the vaccine virus and the majority of representative recent B/Yamagata/16/88 lineage viruses. Geometric mean HI titres to recent B/Victoria/2/87 lineage viruses were reduced (average reductions for B/Victoria/2/87 lineage viruses: adults, 86%; older adults, 74%).


    Recommended composition of influenza virus vaccines for use in the 2014 southern hemisphere influenza season

    A(H1N1)pdm09 viruses co-circulated in varying proportions with A(H3N2) and B viruses during the period of February–September 2013, with outbreaks in several countries. The majority of A(H1N1)pdm09 viruses were antigenically similar to A/California/7/2009. Vaccines containing A/California/7/2009 antigens elicited anti-HA antibodies in humans of similar titres against the vaccine virus and recent A(H1N1)pdm09 viruses.

    Influenza A(H3N2) viruses were associated with outbreaks in several countries. The majority of recent viruses were antigenically and genetically similar to the cell-propagated A/Texas/50/2012 and A/Victoria/361/2011 viruses. Many A(H3N2) viruses isolated since February 2013 were inhibited by ferret antisera raised against egg-propagated A/Texas/50/2012. Vaccines containing A/Texas/50/2012 antigens elicited antibodies of similar geometric mean HI titres to the cell-propagated vaccine virus and the majority of representative recent A(H3N2) viruses.

    Influenza B activity was reported in many countries. The proportion of B/Yamagata/16/88 lineage viruses increased in many parts of the world. The majority of recent B/Victoria/2/87 lineage viruses were antigenically and genetically closely related to B/Brisbane/60/2008. The majority of recently reported B/Yamagata/16/88 viruses belonged to the HA phylogenetic clade 2. Most recently isolated B/Yamagata/16/88 lineage viruses were antigenically similar to B/Massachusetts/2/2012-like (clade 2) viruses.

    Current vaccines containing B/Massachusetts/2/2012 antigens elicited anti-HA antibodies in humans that had similar titres against the vaccine viruses and recent viruses of the B/Yamagata/16/88 lineage.

    Lists of candidate influenza vaccine viruses that are available or under development and reagents for vaccine standardization, including those for this recommendation, can be found on the WHO website.(7) Candidate vaccine viruses for A(H5N1), A(H9N2), A(H7) and A(H3N2)v viruses are updated on the same website.

    As in previous years, national or regional authorities approve the composition and formulation of vaccines used in each country. National public health authorities are responsible for making recommendations regarding the use of the vaccine. WHO has published recommendations on the prevention of influenza.(8)

    Candidate vaccine viruses (including reassortants) and reagents for use in the laboratory standardization of inactivated vaccine may be obtained from:

    (i) Immunobiology, Office of Laboratory and Scientific Services, Monitoring and Compliance Group, Therapeutic Goods Administration, P.O. Box 100, Woden, ACT, 2606, Australia (fax: +61262328564, email: influenza.standards@tga.gov.au; website: http://www.tga.gov.au );

    (ii) Division of Virology, National Institute for Biological Standards and Control, a centre of the Medicines and Healthcare products Regulatory Agency (MHRA), Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK (fax: +441707641050, e-mail: enquiries@nibsc.org, website: http://www.nibsc.ac.uk/spotlight/influenza_resource_centre/reagents.aspx );

    (iii) Division of Biological Standards and Quality Control, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20892, USA (fax: +1 301 480 9748);

    (iv) Center for Influenza Virus Research, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-Murayama, Tokyo 208-0011, Japan (fax: +81425616156, email: flu-vaccine@nih.go.jp ).

    Requests for reference viruses should be addressed to:

    (i) WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, 10 Wreckyn Street, North Melbourne, Victoria 3051, Australia (fax: +61393423939, website: http://www.influenzacentre.org, email: whoflu@influenzacentre.org );

    (ii) WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashi-Murayama, Tokyo 208-0011, Japan (fax: +81425616149 or +81425652498, email: todagiri@nih.go.jp;

    (iii) WHO Collaborating Centre for Surveillance, Epidemiology and Control of Influenza, Centers for Disease Control and Prevention, 1600 Clifton Road, Mail Stop G16, Atlanta, GA 30333, USA (fax: +14046390080, website: http://www.cdc.gov/flu/, email: influenzavirussurveillance@cdc.gov );

    (iv) WHO Collaborating Centre for Reference and Research on Influenza, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK (fax: +442089064477, website: http://www.nimr.mrc.ac.uk/wic/, email: whocc@nimr.mrc.ac.uk );

    (v) WHO Collaborating Centre for Reference and Research on Influenza, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Changping District, 102206, Beijing, P.R. China. (tel: +86 10 5890 0851, fax: +86 10 5890 0851, email: whoccchina@cnic.org.cn, website: http://www.cnic.org.cn/eng/ ).

    Influenza surveillance information is updated on the WHO website.(9)
    __

    It is recommended that vaccines for use in the 2014 influenza season (southern hemisphere winter) contain the following:
    • an A/California/7/2009 (H1N1)pdm09-like virus;a
    • an A/Texas/50/2012 (H3N2)-like virus;b
    • a B/Massachusetts/2/2012-like virus.

    It is recommended that quadrivalent vaccines containing 2 influenza B viruses contain the above 3 viruses and a B/Brisbane/60/2008-like virus.
    __

    a A/Christchurch/16/2010 is an A/California/7/2009-like virus.

    b A/Texas/50/2012 is an A(H3N2) virus that following adaptation to growth in eggs has maintained antigenic properties similar to the majority of recently circulating cell-propagated A(H3N2) viruses including A/Victoria/361/2011.
    ______

    (1) See http://www.who.int/influenza/vaccines/virus/en/, accessed September 2013.

    (2) A description of the process of influenza vaccine virus selection and development is available at: http://www.who.int/gb/pip/pdf_files/Fluvaccvirusselection.pdf, accessed September 2013.

    (3) See http://www.who.int/entity/influenza/human_animal_interface/EN_GIP_20130829CumulativeNumberH5N1cases.pdf, accessed September 2013.

    (4) See http://www.who.int/influenza/human_animal_interface/influenza_h7n9/Data_Reports/en/index.html, accessed September 2013.

    (5) See http://www.cdc.gov/flu/swineflu/h3n2v-situation.htm, accessed September 2013.

    (6) See No. 39, 2012, pp. 369–374.

    (7) See in http://www.who.int/influenza/vaccines/virus/candidates_reagents/home , accessed September 2013.

    (8) See No. 47, 2012, pp. 461–476.

    (9) See http://www.who.int/influenza


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