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TitleDisulfide stabilization of human norovirus GI.1 virus-like particles focuses immune response toward blockade epitopes.
Journal, issue, pagesNPJ Vaccines, Vol. 5, Issue 1, Page 110, Year 2020
Publish dateDec 14, 2020
AuthorsRaffaello Verardi / Lisa C Lindesmith / Yaroslav Tsybovsky / Jason Gorman / Gwo-Yu Chuang / Caitlin E Edwards / Paul D Brewer-Jensen / Michael L Mallory / Li Ou / Arne Schön / Wei Shi / Ena S Tully / George Georgiou / Ralph S Baric / Peter D Kwong /
PubMed AbstractHuman noroviruses are non-enveloped, single-strand RNA viruses that cause pandemic outbreaks of acute gastroenteritis. A bivalent vaccine containing GI.1 and GII.4 virus-like particles (VLPs) has ...Human noroviruses are non-enveloped, single-strand RNA viruses that cause pandemic outbreaks of acute gastroenteritis. A bivalent vaccine containing GI.1 and GII.4 virus-like particles (VLPs) has been shown to be safe and highly immunogenic, but its efficacy and durability have been limited. Here, we show that norovirus GI.1 VLPs are unstable and contain a substantial fraction of dissociated VLP components. Broadly reactive, non-neutralizing antibodies isolated from vaccinated donors bound to the dissociated components, but not to the intact VLPs. Engineering of interprotomer disulfide bonds within the shell domain prevented disassembly of the VLPs, while preserving antibody accessibility to blockade epitopes. Without adjuvant, mice immunized with stabilized GI.1 VLPs developed faster blockade antibody titers compared to immunization with wild-type GI.1 VLPs. In addition, immunization with stabilized particles focused immune responses toward surface-exposed epitopes and away from occluded epitopes. Overall, disulfide-stabilized norovirus GI.1 VLPs elicited improved responses over the non-disulfide-stabilized version, suggesting their promise as candidate vaccines.
External linksNPJ Vaccines / PubMed:33318483 / PubMed Central
MethodsEM (single particle)
Resolution3.86 Å
Structure data

22897

7kjp

EMDB-22897, PDB-7kjp:
Disulfide Stabilized Norovirus GI.1 VLP Shell Region
Method: EM (single particle) / Resolution: 3.86 Å

Source
  • norwalk virus (strain gi/human/united states/norwalk/1968)
KeywordsVIRUS LIKE PARTICLE / Norovirus / Stabilized / VLP / Shell

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