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TitleRational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles.
Journal, issue, pagesNat Commun, Vol. 11, Issue 1, Page 2841, Year 2020
Publish dateJun 5, 2020
AuthorsDaning Wang / Xinlin Liu / Minxi Wei / Ciying Qian / Shuo Song / Jie Chen / Zhiping Wang / Qin Xu / Yurou Yang / Maozhou He / Xin Chi / Shiwen Huang / Tingting Li / Zhibo Kong / Qingbing Zheng / Hai Yu / Yingbin Wang / Qinjian Zhao / Jun Zhang / Ningshao Xia / Ying Gu / Shaowei Li /
PubMed AbstractThe capsid of human papillomavirus (HPV) spontaneously arranges into a T = 7 icosahedral particle with 72 L1 pentameric capsomeres associating via disulfide bonds between Cys175 and Cys428. Here, ...The capsid of human papillomavirus (HPV) spontaneously arranges into a T = 7 icosahedral particle with 72 L1 pentameric capsomeres associating via disulfide bonds between Cys175 and Cys428. Here, we design a capsomere-hybrid virus-like particle (chVLP) to accommodate multiple types of L1 pentamers by the reciprocal assembly of single C175A and C428A L1 mutants, either of which alone encumbers L1 pentamer particle self-assembly. We show that co-assembly between any pair of C175A and C428A mutants across at least nine HPV genotypes occurs at a preferred equal molar stoichiometry, irrespective of the type or number of L1 sequences. A nine-valent chVLP vaccine-formed through the structural clustering of HPV epitopes-confers neutralization titers that are comparable with that of Gardasil 9 and elicits minor cross-neutralizing antibodies against some heterologous HPV types. These findings may pave the way for a new vaccine design that targets multiple pathogenic variants or cancer cells bearing diverse neoantigens.
External linksNat Commun / PubMed:32503989 / PubMed Central
MethodsEM (single particle)
Resolution26.1 Å
Structure data

EMDB-0878:
HPV chVLP
Method: EM (single particle) / Resolution: 26.1 Å

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