Novel mRNA-based VP8* vaccines against rotavirus are highly immunogenic in rodents

Abstract

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 secretedin vitroand 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.

mRNA vaccines expressing malaria transmission-blocking antigens Pfs25 and Pfs230D1 induce a functional immune response

“…Since this difference was not further investigated, we could not conclude if the amount of secreted vs. cell surface retained protein is identical or if total expressed protein amounts differ between the two constructs. Future investigations may examine if this effect could be mediated by protein design approaches leading to nanoparticle formation of secreted proteins as described before 55 .…”

Equine Rotavirus A under the One Health Lens: Potential Impacts on Public Health

“…Thus, several experimental vaccines are currently under development as alternatives. Among these are inactivated, subunit, norovirus nanoparticles expressing rotavirus VP8* proteins, virus-like particles (VLP), and plant-based VLPs expressing several rotavirus capsid proteins and mRNA vaccines [ 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 ].…”