mRNA-based VP8* nanoparticle vaccines against rotavirus are highly immunogenic in rodents.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
22 Dec 2023
22 Dec 2023
Historique:
received:
31
03
2023
accepted:
05
12
2023
medline:
22
12
2023
pubmed:
22
12
2023
entrez:
21
12
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38129390
doi: 10.1038/s41541-023-00790-z
pii: 10.1038/s41541-023-00790-z
doi:
Types de publication
Journal Article
Langues
eng
Pagination
190Subventions
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : INV-020846
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : INV-020846
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : OPP-1126258
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : INV-020846
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : OPP-1126258
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : INV-020846
Informations de copyright
© 2023. The Author(s).
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