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Background Influenza vaccination may provide a “back-boost” to antibodies against previously encountered strains. If the back-boost effect is common, this could allow more aggressive vaccine updates, as emerging variants would be expected to both elicit de-novo responses and boost pre-existing responses against recently circulating strains. Here we used the emergence of an antigenically novel A(H3N2) strain to determine whether an antigenically updated vaccine boosted antibodies against historical strains. Methods We performed hemagglutination-inhibition (HI) assays on pre- and post-vaccination sera from 124 children 5–17 years old who received 2015–2016 inactivated influenza vaccine, containing an antigenically updated A(H3N2) strain. We evaluated the mean fold increase in HI titer against both the 2015–2016 vaccine strain and representative strains from two prior antigenic clusters. Factors associated with post-vaccination titers against historical strains were evaluated using linear regression, adjusting for baseline titer. Results Geometric mean titers against each antigen examined increased significantly after vaccination ( P  < .0001). Mean fold increase was 3.29 against the vaccine strain and 1.22–1.46 against historical strains. Response to vaccine strain was associated with increased post-vaccination titers against historical strains. Conclusions A vaccine containing an antigenically novel A(H3N2) strain modestly boosted antibody responses against historical influenza strains in children. [ABSTRACT FROM AUTHOR]

The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a “mosaic” hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes. Modified vaccinia Ankara (MVA) expressing this H5 mosaic (MVA-H5M) protected mice against multiple homosubtypic H5N1 strains and a heterosubtypic H1N1 virus. To assess its potential as a human vaccine we evaluated the ability of MVA-H5M to provide heterosubtypic immunity to influenza viruses in a non-human primate model. Rhesus macaques received an initial dose of either MVA-H5M or plasmid DNA encoding H5M, followed by a boost of MVA-H5M, and then were challenged, together with naïve controls, with the heterosubtypic virus A/California/04/2009 (H1N1pdm). Macaques receiving either vaccine regimen cleared H1N1pdm challenge faster than naïve controls. Vaccination with H5M elicited antibodies that bound H1N1pdm HA, but did not neutralize the H1N1pdm challenge virus. Plasma from vaccinated macaques activated NK cells in the presence of H1N1pdm HA, suggesting that vaccination elicited cross-reactive antibodies capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). Although HA-specific T cell responses to the MVA-H5M vaccine were weak, responses after challenge were stronger in vaccinated macaques than in control animals. Together these data suggest that mosaic HA antigens may provide a means for inducing broadly cross-reactive immunity to influenza viruses. [ABSTRACT FROM AUTHOR]