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

Daning 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 () and Shaowei Li ()
Additional contact information
Daning Wang: Xiamen University
Xinlin Liu: Xiamen University
Minxi Wei: Xiamen University
Ciying Qian: Xiamen University
Shuo Song: Xiamen University
Jie Chen: Xiamen University
Zhiping Wang: Xiamen University
Qin Xu: Xiamen University
Yurou Yang: Xiamen University
Maozhou He: Xiamen University
Xin Chi: Xiamen University
Shiwen Huang: Xiamen University
Tingting Li: Xiamen University
Zhibo Kong: Xiamen University
Qingbing Zheng: Xiamen University
Hai Yu: Xiamen University
Yingbin Wang: Xiamen University
Qinjian Zhao: Xiamen University
Jun Zhang: Xiamen University
Ningshao Xia: Xiamen University
Ying Gu: Xiamen University
Shaowei Li: Xiamen University

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-16639-1

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