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Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles.
- Source :
-
Nature communications [Nat Commun] 2020 Jun 05; Vol. 11 (1), pp. 2841. Date of Electronic Publication: 2020 Jun 05. - Publication Year :
- 2020
-
Abstract
- The capsid of human papillomavirus (HPV) spontaneously arranges into a Tâ=â7 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.
- Subjects :
- Animals
Antibodies, Neutralizing blood
Antibodies, Neutralizing immunology
Antibodies, Viral blood
Antibodies, Viral immunology
Capsid Proteins administration & dosage
Capsid Proteins genetics
Drug Design
Epitopes genetics
Epitopes immunology
Female
Humans
Immunogenicity, Vaccine
Mice
Models, Animal
Mutation
Neoplasms virology
Neutralization Tests
Papillomaviridae genetics
Papillomavirus Infections virology
Papillomavirus Vaccines administration & dosage
Papillomavirus Vaccines genetics
Protein Multimerization genetics
Protein Multimerization immunology
Vaccines, Virus-Like Particle administration & dosage
Vaccines, Virus-Like Particle genetics
Vaccines, Virus-Like Particle immunology
Capsid Proteins immunology
Neoplasms therapy
Papillomaviridae immunology
Papillomavirus Infections therapy
Papillomavirus Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 32503989
- Full Text :
- https://doi.org/10.1038/s41467-020-16639-1