The potential of the microbiota to influence vaccine responses

Abstract

After clean water, vaccines are the primary public health intervention providing protection against serious infectious diseases. Antigen-specific antibody-mediated responses play a critical role in the protection conferred by vaccination; however these responses are highly variable among individuals. In addition, vaccine immunogenicity is frequently impaired in developing world populations, for reasons that are poorly understood. Although the factors that are associated with interindividual variation in vaccine responses are likely manifold, emerging evidence from mouse models and studies in human populations now suggests that the gut microbiome plays a key role in shaping systemic immune responses to both orally and parenterally administered vaccines. Herein, we review the evidence to date that the microbiota can influence vaccine responses and discuss the potential mechanisms through which these effects may be mediated. In addition, we highlight the gaps in this evidence and suggest future directions for research.

Keywords: B cell; T cell; antibiotics; antibody; short-chain fatty acids.

Figure 1

Mechanisms through which the gut microbiota has been shown to influence antibody responses to vaccination/infection in mice. A) TLR5‐mediating sensing of flagellin from the gut microbiota by Mϕs is necessary for optimal antibody responses in mice to the seasonal influenza vaccine. B) Nod2‐mediated recognition of muramyl dipeptide (MDP) from the gut microbiota by CD11c⁺ DCs is necessary for optimal antibody responses to intranasal immunization of mice with HSA and CT. C) Dietary fiber supports the production of SCFAs by the gut microbiota which promote optimal antibody responses in mice to Citrobacter infection by boosting B cell metabolism and gene expression. D) These positive effects of the microbiota on vaccine responses are abrogated in antibiotic treated or germ‐free mice.