Microbiome-Derived Lipid Nanoparticles for Improved Immunogenicity of mRNA Vaccines

Lipid nanoparticle (LNP)-based mRNA vaccines have achieved great success during the COVID-19 pandemic. However, the current formulation of LNPs requires additional optimization for the improvement of antigen-specific immunity and the vaccination effect. The microbiome and its metabolites have shown beneficial effects on the host immune systems, especially on the induction of antigen-specific T cells and the antibody response of B cells. Herein, microbiome-derived LNPs (mbm-LNPs) are developed via the incorporation of short-chain fatty acids, the microbiome metabolites, into LNPs. mbm-LNPs-mediated delivery of ovalbumin and COVID-19 spike mRNA significantly improves antigen-specific CD8(+) T cell and B cell responses compared to the approved LNP formulation. In vivo study in a tumor model exhibits enhanced protective effects of mbm-LNP against the antigen-expressing tumor cells and generalizes the immune-improving effect of mbm-LNP on the various ionizable lipids. Conclusively, this study suggests that microbiome metabolites could be an adjuvant for improving antigen-specific adaptive immune responses of mRNA vaccines.