7kjp | pdb_00007kjp
Disulfide Stabilized Norovirus GI.1 VLP Shell Region
Structural highlights
Function[CAPSD_NVN68] Capsid protein self assembles to form an icosahedral capsid with a T=3 symmetry, about 38 nm in diameter, and consisting of 180 capsid proteins. A smaller form of capsid with a diameter of 23 nm might be capsid proteins assembled as icosahedron with T=1 symmetry. The capsid encapsulate the genomic RNA and VP2 proteins. Attaches virion to target cells by binding histo-blood group antigens present on gastroduodenal epithelial cells.[1] Soluble capsid protein may play a role in viral immunoevasion.[2] Publication Abstract from PubMedHuman 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. Disulfide stabilization of human norovirus GI.1 virus-like particles focuses immune response toward blockade epitopes.,Verardi R, Lindesmith LC, Tsybovsky Y, Gorman J, Chuang GY, Edwards CE, Brewer-Jensen PD, Mallory ML, Ou L, Schon A, Shi W, Tully ES, Georgiou G, Baric RS, Kwong PD NPJ Vaccines. 2020 Dec 14;5(1):110. doi: 10.1038/s41541-020-00260-w. PMID:33318483[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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