A-910823, a squalene-based emulsion adjuvant, enhances robust and broad immune responses of quadrivalent influenza vaccine in ferrets

Robust and broad protective immunity is typically elicited by co-administration of an adjuvant with vaccine antigens. A-910823, a squalene-based emulsion adjuvant, has been approved in Japan. It effectively enhances the humoral and cellular immunity of S-268019-b, a recombinant COVID-19 vaccine; however, the adjuvant effects of A-910823 on other vaccines, including influenza vaccine, have not been evaluated. Here, a ferret model was employed to investigate the adjuvant effects of A-910823 when combined with split-inactivated quadrivalent influenza vaccine (QIV). We demonstrate that combination of A-910823 with QIV enhances the neutralizing antibody titer and its breadth against non-vaccine strains. Also, the protective efficacy of A-910823-adjuvanted QIV against virus challenge has been confirmed. Of note, QIV combined with A-910823 caused only minor detectable side effects, whereas a significant increase in fever was observed after two doses of mRNA-LNP in ferrets. This study provides information on the effectiveness and safety of A-910823-adjuvanted QIV and suggests the usefulness of the ferret model for evaluating vaccine-induced reactogenicity. •A-910823 enhances immunogenicity and expands the breadth of neutralizing antibody of quadrivalent influenza vaccine in ferrets.•A-910823 enhances the protective efficacy of QIV against influenza virus challenge in ferrets.•A-910823-adjuvanted QIV displayed detectable levels of fever following one dose but not two doses of vaccination in ferrets.•Ferrets showed a significant increase in fever following immunization with one or two doses of mRNA-LNP.