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Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles

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 b...

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Autores principales: Wang, Daning, Liu, Xinlin, Wei, Minxi, Qian, Ciying, Song, Shuo, Chen, Jie, Wang, Zhiping, Xu, Qin, Yang, Yurou, He, Maozhou, Chi, Xin, Huang, Shiwen, Li, Tingting, Kong, Zhibo, Zheng, Qingbing, Yu, Hai, Wang, Yingbin, Zhao, Qinjian, Zhang, Jun, Xia, Ningshao, Gu, Ying, Li, Shaowei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275066/
https://www.ncbi.nlm.nih.gov/pubmed/32503989
http://dx.doi.org/10.1038/s41467-020-16639-1
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author Wang, Daning
Liu, Xinlin
Wei, Minxi
Qian, Ciying
Song, Shuo
Chen, Jie
Wang, Zhiping
Xu, Qin
Yang, Yurou
He, Maozhou
Chi, Xin
Huang, Shiwen
Li, Tingting
Kong, Zhibo
Zheng, Qingbing
Yu, Hai
Wang, Yingbin
Zhao, Qinjian
Zhang, Jun
Xia, Ningshao
Gu, Ying
Li, Shaowei
author_facet Wang, Daning
Liu, Xinlin
Wei, Minxi
Qian, Ciying
Song, Shuo
Chen, Jie
Wang, Zhiping
Xu, Qin
Yang, Yurou
He, Maozhou
Chi, Xin
Huang, Shiwen
Li, Tingting
Kong, Zhibo
Zheng, Qingbing
Yu, Hai
Wang, Yingbin
Zhao, Qinjian
Zhang, Jun
Xia, Ningshao
Gu, Ying
Li, Shaowei
author_sort Wang, Daning
collection PubMed
description 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.
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spelling pubmed-72750662020-06-16 Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles Wang, Daning Liu, Xinlin Wei, Minxi Qian, Ciying Song, Shuo Chen, Jie Wang, Zhiping Xu, Qin Yang, Yurou He, Maozhou Chi, Xin Huang, Shiwen Li, Tingting Kong, Zhibo Zheng, Qingbing Yu, Hai Wang, Yingbin Zhao, Qinjian Zhang, Jun Xia, Ningshao Gu, Ying Li, Shaowei Nat Commun Article 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. Nature Publishing Group UK 2020-06-05 /pmc/articles/PMC7275066/ /pubmed/32503989 http://dx.doi.org/10.1038/s41467-020-16639-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Daning
Liu, Xinlin
Wei, Minxi
Qian, Ciying
Song, Shuo
Chen, Jie
Wang, Zhiping
Xu, Qin
Yang, Yurou
He, Maozhou
Chi, Xin
Huang, Shiwen
Li, Tingting
Kong, Zhibo
Zheng, Qingbing
Yu, Hai
Wang, Yingbin
Zhao, Qinjian
Zhang, Jun
Xia, Ningshao
Gu, Ying
Li, Shaowei
Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles
title Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles
title_full Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles
title_fullStr Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles
title_full_unstemmed Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles
title_short Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles
title_sort rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275066/
https://www.ncbi.nlm.nih.gov/pubmed/32503989
http://dx.doi.org/10.1038/s41467-020-16639-1
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