Assessment of enhanced influenza vaccination finds that FluAd conveys an advantage in mice and older adults.

Enhanced inactivated influenza vaccines (eIIV) aim to increase immunogenicity and protection compared with the widely used standard IIV (S-IIV). We tested four vaccines in parallel, FluZone high dose, FluBlok and FluAd versus S-IIV in a randomised controlled trial of older adults and in a mouse infection model to assess immunogenicity, protection from lethal challenge and mechanisms of action. In older adults, FluAd vaccination stimulated a superior antibody profile, including H3-HA antibodies that were elevated for up to 1 year after vaccination, higher avidity H3HA IgG and larger HA stem IgG responses. In a mouse model, FluAd also elicited an earlier and larger induction of HA stem antibodies with increased germinal centre responses and upregulation and long-term expression of B-cell switch transcription factors. Long-term cross-reactive memory responses were sustained by FluAd following lethal heterosubtypic influenza challenge, with reduced lung damage and viral loads, coinciding with increased T- and B-cell recall. Advantages were also noted for the high-dose FluZone vaccine in both humans and mice. The early, broadly reactive and long-lived antibody response of FluAd indicates a potential advantage of this vaccine, particularly in years when there is a mismatch between the vaccine strain and the circulating strain of influenza viruses.