Noroviruses are a leading cause of acute gastroenteritis across all age groups, associated with ∼18% of diarrheal disease globally. Infections span a broad clinical spectrum, ranging from asymptomatic and self-limiting illnesses to hospitalizations and deaths. No preventive vaccines or targeted therapies are currently available. In this study, we designed vaccine candidates containing mRNAs encoding norovirus VP1 proteins of genotypes GI.1, GII.2, GII.3, GII.4, and GII.6, and evaluated their immunogenicity in mice and nonhuman primates (NHPs). In mice, all five mRNAs, dosed separately or together, elicited serum IgG antibodies that bound to norovirus virus-like particles (VLPs), serum antibodies that blocked the binding of VLPs to histo-blood group antigens (HBGAs), and norovirus-specific T cell responses. In NHPs, a pentavalent vaccine candidate induced strong humoral and cellular immune responses against each genotype included in the vaccine. Furthermore, compared to VLPs, mRNAs induced similar levels of humoral and cellular responses and comparable levels of durability, as measured by serum antibody titers. Our results indicate that a multivalent mRNA vaccine candidate encoding norovirus VP1 proteins is immunogenic in preclinical models and is a promising candidate to be evaluated in clinical trials.
mRNA Technology