Abstract

We developed nucleoside-modified mRNA-lipid nanoparticle (LNP) vaccines encoding the glycoprotein precursor (GPC) of lymphocytic choriomeningitis virus (LCMV) Armstrong 53b or Clone 13 and evaluated their immunogenicity and protective efficacy. Vaccine quality was assessed by physicochemical characterization of the mRNA-LNP formulations and in vitro antigen expression assays. Immunogenicity was examined in BALB/c mice after monovalent or bivalent immunization by measuring GPC-specific binding antibodies, IgG subclasses, pseudovirus neutralization, and interferon-γ ELISpot responses to GPC peptide pools. Protective efficacy was further assessed in C57BL/6J mice immunized with monovalent vaccines and challenged intravenously with LCMV Clone 13, followed by longitudinal monitoring of body weight and splenic viral loads. Both vaccine candidates showed favorable formulation quality and supported robust antigen expression in vitro. Immunization induced strong GPC-specific binding antibody responses with an IgG2a-dominant subclass pattern and measurable pseudovirus-neutralizing activity. Cellular responses were readily detected in all vaccinated groups and were mainly directed against strain-shared peptide pools. In the Clone 13 challenge model, vaccination reduced disease severity and accelerated splenic viral clearance compared with controls. These findings show that LCMV GPC mRNA-LNP vaccination elicits coordinated humoral and cellular immune responses and provides measurable protection against Clone 13 challenge, supporting further evaluation of this non-infectious platform for LCMV vaccine development.