Key result
The trivalent LS-P2-VP8* mRNA vaccine induced robust, long-lasting homotypic and heterotypic neutralizing antibody responses in rodents, performing equally or better than the corresponding protein vaccines.
Why the study?
Despite oral live-attenuated vaccines, rotavirus remains a leading cause of severe childhood diarrhea, driving demand for parenteral vaccine candidates.
A novel trivalent LS-P2-VP8* mRNA vaccine demonstrates robust and long-lasting immunogenicity in rodents, representing a promising next-generation parenteral rotavirus vaccine candidate.
mRNA VP8* candidates extend protein vaccine platforms; leaves open clinical efficacy and safety in humans.
Despite the availability of live-attenuated oral vaccines, rotavirus remains a major cause of severe childhood diarrhea worldwide. Due to the growing demand for parenteral rotavirus vaccines, we developed novel mRNA-based vaccine candidates targeting the viral spike protein VP8*. Our monomeric P2 (universal T cell epitope)-VP8* mRNA design is equivalent to a protein vaccine currently in clinical development, while LS (lumazine synthase)-P2-VP8* was designed to form nanoparticles. Cyro-electron microscopy and western blotting-based data presented here suggest that proteins derived from LS-P2-VP8* mRNA are secreted in vitro and self-assemble into 60-mer nanoparticles displaying VP8*. mRNA encoded VP8* was immunogenic in rodents and introduced both humoral and cellular responses. LS-P2-VP8* induced superior humoral responses to P2-VP8* in guinea pigs, both as monovalent and trivalent vaccines, with encouraging responses detected against the most prevalent P genotypes. Overall, our data provide evidence that trivalent LS-P2-VP8* represents a promising mRNA-based next-generation rotavirus vaccine candidate.
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Roier et al. (2023) studied Rotavirus. LS-P2-VP8* mRNA vaccine vs. P2-VP8* protein vaccine or sham was evaluated on Immunogenicity (IgG and neutralizing antibody titers). The trivalent LS-P2-VP8* mRNA vaccine induced robust, long-lasting homotypic and heterotypic neutralizing antibody responses in rodents, performing equally or better than the corresponding protein vaccines.
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