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

Posted: 2020-06-19   Visits: 11


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.


Source: https://life.xmu.edu.cn/lifeen/2020/0618/c8819a405215/page.htm

Link: https://www.nature.com/articles/s41467-020-16639-1