S1) and a group of viruses that appeared to be circulating exclusively in West Africa, as represented by A/Dakar/20/2012 (Fig. 2). AA substitutions in the 153–157 region of HA1 were Tanespimycin solubility dmso identified in a number of cell- or egg-propagated A(H1N1)pdm09 viruses that had low reactivity to ferret antisera raised against A/California/7/2009 and some viruses had nucleotide polymorphism

in their HA sequences encoding these amino acids (for example A/Beijing-Huairou/SWL11293/2013, Table 2). Generally, these 153–157 substitutions/polymorphisms were not detected in the original clinical samples, indicating that they had arisen or become predominant during adaptation to culture. Sequences of isolates with substitutions at positions 153–157 in the HA were distributed throughout the phylogenetic tree and have appeared in nearly all genetic groups in the past (data not shown). Full genome sequencing was carried out on viruses from several geographic regions and no evidence of reassortment with co-circulating A(H3N2) viruses or other viruses was obtained (data not shown). PD-0332991 clinical trial Antigenic cartography illustrated that the majority of A(H1N1)pdm09 isolates continued to be antigenically similar to A/California/7/2009 and clustered together, demonstrating little antigenic diversity during this period or since

2009 (Fig. S2). In contrast many of the viruses with AA substitutions in the 153–157 region of HA1 clustered together at some antigenic distance from the vaccine virus A/California/7/2009 and most other recent isolates (Fig. S2, Table 2). Vaccines containing the A/California/7/2009 (H1N1pdm09) antigen stimulated anti-HA antibodies second of similar geometric mean HI titres to the vaccine virus and the majority

of representative A(H1N1)pdm09 isolates tested. Fig. S3 summarises human serology following seasonal influenza vaccination. Only a few A(H1N1)pdm09 viruses showed a significant (>50%) reduction in geometric mean titres (GMT) in HI tests with human sera from vaccinees who received vaccines containing A/California/7/2009. In some panels reductions were seen against egg-derived A/Bangladesh/2021/2012 virus which has an N156S substitution in HA1, a change known to alter the antigenic properties of H1N1pdm09 viruses, as described above. Although reactivity was also reduced against some cell-propagated viruses, such as A/Stockholm/34/2012, no reduction was seen in HI studies of this virus using post-infection ferret antiserum. Based on analyses of data presented at the VCM, it was concluded that the observed genetic diversity of A(H1N1)pdm09 viruses had not resulted in changes in their antigenic properties and that A/California/7/2009, remained appropriate for use in the 2013–2014 Northern Hemisphere vaccine. The majority (61.