Distinctive innate immune signatures at the injection site predict the adjuvant-mediated boost of adaptive responses towards a flu subunit vaccine. (106.9)

Abstract

Abstract Vaccine adjuvants activate specific innate immune pathways which boost the adaptive responses to co-administered antigens, but the efficacy of adjuvants is often antigen-dependent. Recently, several human studies have shown that oil-in-water emulsions such as MF59 are superior to alum in enhancing the response to flu subunit vaccines. However, the mechanism of action of flu adjuvanticity is not fully understood. In this study we wanted to identify the innate immune signatures that are associated to adjuvanticity to flu subunit vaccine in the mouse model. First, we immunized mice with seasonal trivalent flu antigens or tetanus toxoid (TT) mixed with MF59, alum or three TLR-dependent adjuvants: CpG (TLR9), resiquimod (TLR7/8) and Pam3CSK4 (TLR2). All adjuvants were similarly efficient in inducing an adaptive immune response to TT. By contrast, MF59 and, to a lesser extent, Pam3CSK4 enhanced the antibody responses to HA. In order to correlate innate immune gene signatures induced by the vaccine adjuvants with the ability to boost flu adaptive responses, we performed microarray analysis with the same set of adjuvants both in vitro in mouse splenocytes and in vivo in mouse muscle and draining lymph nodes. In summary, we show that strong activation of innate immunity in the muscle, but not in draining LNs, and local recruitment of CD11b+ blood cells at injection site by MF59 and TLR2 vaccine adjuvants correlate with their ability to enhance antibody responses to flu antigens.