Distinct components of nucleoside-modified messenger RNA vaccines cooperate to instruct efficient germinal center responses 2950

Abstract Description Nucleoside-modified mRNA vaccines elicit protective antibodies through their ability to promote T follicular helper (Tfh) cells. The lipid nanoparticle (LNP) component of mRNA vaccines possesses inherent adjuvant activity. However, to what extent nucleic acid can be sensed and contribute to Tfh cell responses remains largely undefined. Herein, we deconvoluted the signals induced by LNP and nucleic acid that instruct dendritic cells (DCs) to promote Tfh cell differentiation. We demonstrated that the nucleic acid drives the production of type I interferons that act on DCs to induce their maturation and the induction of Th1-biased Tfh responses. Conversely, LNP favors the acquisition of a Tfh cell-inducing program in DCs, a stronger Th2 polarization in Tfh cells, and allows for rapid mRNA translation by DCs within the draining lymph node. Our work unravels distinct adjuvant features of mRNA vaccines necessary for the induction of Tfh cells, with implications for vaccine design. Funding Sources Supported by the National Institute of Allergy and Infectious Diseases (NIAID R01AI168312) Topic Categories Vaccines and Immunotherapy (VAC)