Targeting Gut Microbial Composition to Enhance Vaccine Efficacy

Influenza remains a substantial public health burden with significant rates of morbidity, mortality and economic loss. The efficacy of influenza vaccination is not complete and could be improved. Toll like receptors (TLR) play an important role in promoting antibody responses and can act to adjuvant vaccine-induced antibody responses. Furthermore, recently has been demonstrated that TLR mediated sensing of gut microbiota is required for influenza-vaccine induced antibody responses. Therefore we investigated TLR responses in two lines of BALB/c mice with divergent gut microbial compositions that have marked differences in baseline antibody production. These mice showed significant differences in serum concentrations of IFN-γ, MCP-1 and IL-12p70, especially 6h following systemic LPS or CpG administration. Furthermore, symptoms of septic shock including body temperature were affected. Vaccination with trivalent inactivated influenza vaccine (TIV) resulted in markedly different primary and secondary (5 days post boost) immune responses measured as TIV-specific antibody titers. In addition, antibody responses to influenza infection varied significantly between these two lines of mice with different microbiota. Therefore we suggest modulation of the microbiota, e.g. with dietary components, as an effective approach to improve vaccine-mediated protection against influenza.