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

• DOI: 10.1038/s41467-020-16639-1
• Publication Date: 2020-06-05T10:04:22Z
• Authors: 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; Shaowei Li
• Keywords: Pentamer; Capsomere; Virus-like particle

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 capsomere-hybrid virus-like (chVLP) to accommodate multiple types pentamers by the reciprocal assembly single C175A C428A mutants, either which alone encumbers pentamer self-assembly. We show that co-assembly any pair mutants across at least nine HPV genotypes occurs preferred equal molar stoichiometry, irrespective type or number sequences. A nine-valent chVLP vaccine—formed through structural clustering epitopes—confers neutralization titers are comparable Gardasil 9 elicits minor cross-neutralizing antibodies against some heterologous types. These findings may pave way for new vaccine targets pathogenic variants cancer cells bearing diverse neoantigens.