8F25

Cryo-EM structure of Lumazine synthase nanoparticle linked to VP8* antigen

Summary for 8F25

• Entry DOI: 10.2210/pdb8f25/pdb
• EMDB information: 28807
• Descriptor: 6,7-dimethyl-8-ribityllumazine synthase (1 entity in total)
• Functional Keywords: rotavirus, vp8*, lumazine synthase, nanoparticle, viral protein
• Biological source: Aquifex aeolicus
• Total number of polymer chains: 60
• Total formula weight: 1003691.16

Authors

Mangala Prasad, V.,Lee, K.K. (deposition date: 2022-11-07, release date: 2023-04-12, Last modification date: 2024-01-10)

Primary citation

Roier, S.,Mangala Prasad, V.,McNeal, M.M.,Lee, K.K.,Petsch, B.,Rauch, S.
mRNA-based VP8* nanoparticle vaccines against rotavirus are highly immunogenic in rodents.
Npj Vaccines, 8:190-190, 2023

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 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.

PubMed: 38129390
DOI: 10.1038/s41541-023-00790-z

Experimental method

ELECTRON MICROSCOPY (2.6 Å)