A novel recombinant adjuvant replacing the CD4+ T helper cell functions in inducing IgG isotype antibodies and protection by T cell dependent influenza split vaccines (VAC8P.1052)

The action mechanisms of adjuvants have not been well understood yet. We hypothesized that an effective adjuvant would overcome a defect in CD4+ T cell help for the induction of immune responses and protection by T cell dependent vaccines. We found that current influenza split vaccine was not able to induce antibodies and protection in a CD4+ T cell deficient condition. In an attempt to develop an effective adjuvant, we developed a recombinant virus-like particle expressing flagellin (FliC-VLP) and investigated its adjuvant effects and mechanisms by comparing alum adjuvant. CD4 knockout (CD4KO) mice that were immunized with influenza split vaccine plus FliC-VLP (or MF59, AS04 human adjuvant) induced IgG isotype-switched antibodies, germinal center formation, and virus-specific memory cells, all of which were not induced in CD4KO mice with split vaccine alone. Levels of antibodies and protective efficacy in CD4KO mice with split vaccine plus FliC-VLP were significantly higher than those in C57BL/6 wild type mice without adjuvant and CD4KO mice adjuvanted by alum. The adjuvanticity of FliC-VLP was partially dependent on TLR5 when tested in TLR5KO mice. Taken together, the results provide evidence that FliC-VLP adjuvant can stimulate the induction of antigen-specific immune responses and improve protection against lethal infection in CD4KO mice immunized with T cell dependent split vaccines, indicating CD4+ T cell independent action mechanisms of adjuvant.