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MRC (Mill Hill) Sept. 2011 Interim Report

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  • MRC (Mill Hill) Sept. 2011 Interim Report

    Report prepared for the WHO annual consultation on the composition of influenza vaccine for the Southern Hemisphere
    26th ? 30th September 2011
    (snips)

    The majority of H1N1 viruses were antigenically similar to the vaccine virus with 13% of viruses showing a >4-fold reduction in HI titre compared with the titre of the vaccine virus (A/California/7/2009) with its homologous postinfection ferret antiserum.

    ...D222X are also marked (on the phylogenetic tree), as is the substitution Q223R associated with the isolation and passage of virus in hens? eggs. Single amino acid substitutions or amino acid polymorphisms between residues 154 to 156 continue to be observed, but not exclusively associated with the propagation of virus in MDCK-SIAT cells, and occur in all genetic groups. Viruses carrying these substitutions frequently showed reduced titres in HI assays with several sera but reductions with the antiserum raised against the vaccine virus, A/California/7/2009, were frequently < 4-fold reductions fall into each genetic group. In genetic group 3, defined by the HA1 amino acid substitutions A134T and S183P and represented by five viruses here, three, which also carry A141S and I295V in HA1 and V152A in HA2, show reduced reactivity with antiserum raised against the vaccine virus. Two of the three viruses also carry polymorphism at 155 of HA1. This group is not new and does not have a strong presence among viruses circulating recently, but previously it had not been identified as being antigenically distinct from the vaccine virus.

    HA genes of recent H1N1 viruses clustered into seven main genetic groups that can be defined by encoded amino acid substitutions:
    (2) N31D, S162N (resulting in the gain of a glycosylation site) & A186T, e.g. A/Czech Republic/32/2011;
    (3) A134T & S183P, e.g. A/Hong Kong/3934/2011;
    (4) N125D, e.g. A/Christchurch/16/2010;
    (5) D97N, R205K, I216V & V249L, e.g. A/Astrakhan/1/2011;
    (6) D97N & S185T, e.g. A/St Petersburg/27/2011;
    (7) D97N, S143G, S185T & A197T, e.g. A/St Petersburg/100/2011;
    (8) A186T & V272A, e.g. A/Ghana/601/2011.

    Viruses collected in June and July 2011 fall into groups 6 and 7.

    Viruses that carry HA genes of genetic group 3, albeit represented in small numbers, show evidence of antigenic divergence from the vaccine virus although this group also contains viruses with polymorphism at residue 155 of the HA. This divergence was not observed in the analyses carried out for the previous influenza vaccine selection meeting.

    H3N2

    Approximately one third (33%) of the viruses showed 8-fold or lower reactivity in the HI assay with antiserum raised against the vaccine virus A/Perth/16/2009. The majority of viruses that showed reduced activity with this antiserum showed improved titres with some of the other antisera, relative to that with the homologous viruses against which the antisera were raised: notably with antisera raised against A Wisconsin/15/2009, A/Alabama/5/2010 and A/Perth/10/2010 - representatives of both the genetic clades of H3N2 viruses currently circulating. Generally there was low reactivity, compared with the reactivity of the homologous virus, with antisera raised against A Victoria/208/2009 and A/Victoria/210/2009, two viruses that often show high homologous titres in HI assays carried out at the London CC.

    Six genetic groups for the HA gene can be seen in circulating H3N2 viruses. Within the A/Perth/16/2009 genetic clade there are two genetic groups defined by amino acid substitutions:

    (1) P162S, I260M & R261Q, e.g. A/Victoria/210/2009 with some viruses also carrying the substitutions E50K, e.g. A/Norway/1186/2011, or N81D, e.g. A/Niigata/510/2011;

    (2) N133D (resulting in the loss of a glycosylation site), R142G, T212A &V213A, this group is not represented in our recently collected viruses and is not shown in Figure 11, page X.

    Four genetic groups, in two recognizable clusters, can be defined in the A/Victoria/208/2009 genetic clade of H3N2 viruses by amino acid substitutions additional to those that distinguish viruses of the A Victoria/208/2009 clade from those in the A/Perth/16/2009 clade (K62E, K144N & T212A).

    (3) V223I often with N145S, e.g. A/Johannesburg/73/2011; this group canbe divided into two subgroups of viruses, with one sub-group having the substitution N144D (resulting in the loss of a glycosylation site), e.g. A/Stockholm/18/2011, the other sub-group having A198S often with S45 (resulting in the gain of a glycosylation site), T48I and N312S, e.g. A/Hong Kong/3969/2011;

    (4) N312S, e.g. A/Brisbane/11/2010, with many viruses also carrying T48A & K92R, e.g. A/Rhode Island/01/2010 and A Massachusetts/08/2011;

    (5) D53N, Y94H, I230V & E280A, e.g. the reference virus A/Perth/10/2010, with some viruses also carrying the substitution I192T, e.g. A/Athens/108/2011;

    (6) D53N, Y94H, I230V & E280A, as in genetic group 5 but with S199A, e.g. the reference virus A/Iowa/19/2010, and some with S45N (resulting in the gain of a glycosylation site), e.g. A/Hong Kong/3951/2011;

    A further cluster of viruses, defined by S45N (resulting in the gain of a glycosylation site), is represented particularly by recently circulating South African viruses, e.g. A/Johannesburg/114/2011; some viruses also carry L3F & L59I substitutions, e.g. A Norway/685/2011; this cluster has not yet been defined as a distinct genetic group.
    Recent viruses fell into each genetic group; those that showed low reactivity in the in the HI tables distributed into:
    ? group 1 with the substitution E50K,
    ? group 3 with the loss of glycosylation at 144, or the substitution N145S
    ? group 5
    ? group 6
    ? the cluster defined by the substitution S45N, above.

    Conclusion. Antigenic analysis by HI carried out in the presence of oseltamivir showed that one third of viruses had reduced titre with the antiserum raised against the vaccine virus. Virus neutralisation assays of a small number of viruses, that included viruses of different genetic groups some of which had low reactivity in HI assays, showed good reactivity with the antiserum raised against the vaccine virus. There is no evidence from our results that viruses showing low reactivity with antisera raised against the vaccine virus, or viruses genetically similar to the vaccine virus, predominate in any of the emerging genetic groups.

    http://www.nimr.mrc.ac.uk/documents/...t-sep-2011.pdf
    The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

  • #2
    Re: MRC (Mill Hill) Sept. 2011 Interim Report

    GS's groups for H1N1:

    H1N1,2011
    India/UK:144,478,605,640,1056,1171
    2):340,579,605,1056,1171
    3):536,605,1056,1171
    chi1:142,396,536,607,681,865,903,957,1080,1233,
    chi2:135,142,207,282,396,462,489,536,607,681,865,9 03,957,1080,1213,1233
    HK/2213:357,390.433,539,546,647
    Tunisia:451,598,
    Bangkok:183,340,348,552,665,697,7961171

    ***********************

    GS's paired with Mill Hll's:

    (2) N31D (142), S162N (536) & A186T (607), e.g. A/Czech Republic/32/2011
    chi1: 142, 396, 536, 607, 681, 865, 903, 957, 1080, 1233

    (3) A134T (451) & S183P (598), e.g. A/Hong Kong/3934/2011
    Tunisia: 451, 598

    (4) N125D (424), e.g. A/Christchurch/16/2010
    gs has no group for this; N125D was also found in England

    (5) D97N (340), R205K (665), I216V (697) & V249L (796), e.g. A/Astrakhan/1/2011
    Bangkok:183, 340, 348, 552, 665, 697, 796, 1171

    (6) D97N (340) & S185T (605), e.g. A/St Petersburg/27/2011
    India/UK 2): 340, 579, 605, 1056, 1171

    (7) D97N (340), S143G (478), S185T (605) & A197T (640), e.g. A/St Petersburg/100/2011
    India/UK: 144, 478, 605, 640, 1056, 1171
    India/Uk 3): 536, 605, 1056, 1171

    (8) A186T (607) & V272A (865), e.g. A/Ghana/601/2011.
    chi2: 135, 142, 207, 282, 396, 462, 489, 536, 607, 681, 865, 903, 957, 1080, 1213, 1233
    The salvage of human life ought to be placed above barter and exchange ~ Louis Harris, 1918

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