
doi: 10.2139/ssrn.6172559
Rotavirus A(RVA) is a major cause of severe gastroenteritis in infants and young children worldwide. In the absence of effective antiviral treatments, vaccination remains the primary means of disease prevention. Although live oral RV vaccines are available, mRNA vaccines provide notable advantages as a nonreplicating and noninfectious platform, enabling rapid design, precise antigen selection, and more consistent immunogenicity across populations. In this study, a lipid nanoparticle (LNP)–formulated mRNA vaccine encoding the VP7 and VP8 derived from the predominant RVA genotype G9P[8] antigens was generated. The 5′ untranslated region derived from a human RVA isolate was incorporated to enhance translational efficiency. Following LNP encapsulation and formulation at defined ratios, the VP7–VP8 mRNA vaccine was evaluated in BALB/c mice. Two doses induced strong humoral and cellular immunity, including RVA-specific IgG, cross-neutralizing antibodies, and robust T-lymphocyte activation. Protective efficacy was further assessed in a neonatal mouse model. Maternal antibodies elicited by vaccination effectively suppressed viral replication in suckling pups and alleviated intestinal pathology. These findings demonstrate the feasibility of a multivalent RVA mRNA vaccine and provide a foundation for the development of next-generation parenterally administered RV vaccines.
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