mRNA-adjuvanted Influenza A Vaccine Can Induce High Cellular Immunity and Cross Reactivity in Mice

Abstract In recent years, the great success of mRNA-based vaccines for SARS-CoV-2 revealed a potential future for safe and effective mRNA vaccine designs. Given the flexibility and accessibility of mRNA designs, adjuvants in mRNA forms may be applied to enhance immune response and generate better cross-protection. In this study, we fabricated an Influenza mRNA lipid nanoparticle (LNP) vaccine with Influenza A/Aichi/2/1968 (Aichi, H3N2) Hemagglutinin (HA) mRNA and cytokine-adjuvant mRNA (GIFT4 or CCL27). We found that two doses of immunization with mRNA-adjuvanted LNPs induced increased antigen-specific antibody titer and effective protection against Influenza A viruses in mice. The supplement of cytokine mRNAs (GIFT4 or CCL27) provided more robust immunogenicity, including more IL-4 and IFN-γ secreting T cells in the spleen and more IgG and IgA-secreting B cells in the bone marrow. The cytokine mRNA adjuvants also induced early activation of T and B cells in germinal centers. Thus, GIFT4 and CCL27 mRNAs are potential adjuvants for Influenza A mRNA vaccine to elicit higher and broader immune responses in mice.