Search

Eliciting broadly protective antibodies is a critical goal for the development of more effective vaccines against influenza. Optimizing protection is of particular importance in newborns, who are highly vulnerable to severe disease following infection. An effective vaccination strategy for this population must surmount the challenges associated with the neonatal immune system as well as mitigate the inherent immune subdominance of conserved influenza virus epitopes, responses to which can provide broader protection. Here, we show that prime-boost vaccination with a TLR7/8 agonist (R848)-conjugated influenza A virus vaccine elicits antibody responses to the highly conserved hemagglutinin stem and promotes rapid induction of virus neutralizing stem-specific antibodies following viral challenge. These findings support the efficacy of R848 as an effective adjuvant for newborns and demonstrate its ability to enhance antibody responses to subdominant antigenic sites in this at-risk population. [ABSTRACT FROM AUTHOR]

Objectives: Enhanced inactivated influenza vaccines (eIIV) aim to increase immunogenicity and protection compared with the widely used standard IIV (S‐IIV). Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]