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-Structure paper
Title | mRNA-based VP8* nanoparticle vaccines against rotavirus are highly immunogenic in rodents. |
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Journal, issue, pages | NPJ Vaccines, Vol. 8, Issue 1, Page 190, Year 2023 |
Publish date | Dec 22, 2023 |
Authors | Sandro Roier / Vidya Mangala Prasad / Monica M McNeal / Kelly K Lee / Benjamin Petsch / Susanne Rauch / |
PubMed 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 ...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 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. |
External links | NPJ Vaccines / PubMed:38129390 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.6 Å |
Structure data | EMDB-28807, PDB-8f25: |
Source |
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Keywords | VIRAL PROTEIN / Rotavirus / VP8* / lumazine synthase / nanoparticle |