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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Published inNature communications Vol. 11; no. 1; p. 2841
Main Authors 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
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 05.06.2020
Nature Publishing Group
Nature Portfolio
Subjects
101/28
631/250/590/2294
631/326/596/2560
631/45/612/1256
82/80
82/83
Animals
Antibodies
Antibodies, Neutralizing - blood
Antibodies, Neutralizing - immunology
Antibodies, Viral - blood
Antibodies, Viral - immunology
Capsid Proteins - administration & dosage
Capsid Proteins - genetics
Capsid Proteins - immunology
Clustering
Design
Disulfide bonds
Drug Design
Epitopes
Epitopes - genetics
Epitopes - immunology
Female
Genotypes
Human papillomavirus
Humanities and Social Sciences
Humans
Icosahedral phase
Immunogenicity, Vaccine
Mice
Models, Animal
multidisciplinary
Mutants
Mutation
Neoantigens
Neoplasms - therapy
Neoplasms - virology
Neutralization
Neutralization Tests
Neutralizing
Papillomaviridae - genetics
Papillomaviridae - immunology
Papillomavirus Infections - therapy
Papillomavirus Infections - virology
Papillomavirus Vaccines - administration & dosage
Papillomavirus Vaccines - genetics
Papillomavirus Vaccines - immunology
Protein Multimerization - genetics
Protein Multimerization - immunology
Science
Science (multidisciplinary)
Self-assembly
Sequences
Stoichiometry
Vaccines
Vaccines, Virus-Like Particle - administration & dosage
Vaccines, Virus-Like Particle - genetics
Vaccines, Virus-Like Particle - immunology
Virus-like particles
Viruses
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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. An effective vaccine for human papillomavirus (HPV) needs to protect from several genotypes. Here, Wang et al. provide a strategy to produce single capsomere-hybrid virus-like particle (chVLP) composed of capsomers of different genotypes and show that a nona-type chVLP induces similar levels of neutralizing antibodies as an approved HPV vaccine.
AbstractList 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.
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. An effective vaccine for human papillomavirus (HPV) needs to protect from several genotypes. Here, Wang et al. provide a strategy to produce single capsomere-hybrid virus-like particle (chVLP) composed of capsomers of different genotypes and show that a nona-type chVLP induces similar levels of neutralizing antibodies as an approved HPV vaccine.
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.
An effective vaccine for human papillomavirus (HPV) needs to protect from several genotypes. Here, Wang et al. provide a strategy to produce single capsomere-hybrid virus-like particle (chVLP) composed of capsomers of different genotypes and show that a nona-type chVLP induces similar levels of neutralizing antibodies as an approved HPV vaccine.
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.An effective vaccine for human papillomavirus (HPV) needs to protect from several genotypes. Here, Wang et al. provide a strategy to produce single capsomere-hybrid virus-like particle (chVLP) composed of capsomers of different genotypes and show that a nona-type chVLP induces similar levels of neutralizing antibodies as an approved HPV vaccine.
ArticleNumber 2841
Author Wang, Yingbin
Xu, Qin
Wang, Zhiping
Zheng, Qingbing
Wang, Daning
Gu, Ying
Qian, Ciying
Song, Shuo
Yang, Yurou
Xia, Ningshao
Liu, Xinlin
Chen, Jie
Yu, Hai
He, Maozhou
Li, Tingting
Li, Shaowei
Wei, Minxi
Chi, Xin
Zhao, Qinjian
Huang, Shiwen
Kong, Zhibo
Zhang, Jun
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/32503989$$D View this record in MEDLINE/PubMed
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Snippet The capsid of human papillomavirus (HPV) spontaneously arranges into a T = 7 icosahedral particle with 72 L1 pentameric capsomeres associating via disulfide...
Abstract The capsid of human papillomavirus (HPV) spontaneously arranges into a T = 7 icosahedral particle with 72 L1 pentameric capsomeres associating via...
An effective vaccine for human papillomavirus (HPV) needs to protect from several genotypes. Here, Wang et al. provide a strategy to produce single...
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SubjectTerms 101/28
631/250/590/2294
631/326/596/2560
631/45/612/1256
82/80
82/83
Animals
Antibodies
Antibodies, Neutralizing - blood
Antibodies, Neutralizing - immunology
Antibodies, Viral - blood
Antibodies, Viral - immunology
Capsid Proteins - administration & dosage
Capsid Proteins - genetics
Capsid Proteins - immunology
Clustering
Design
Disulfide bonds
Drug Design
Epitopes
Epitopes - genetics
Epitopes - immunology
Female
Genotypes
Human papillomavirus
Humanities and Social Sciences
Humans
Icosahedral phase
Immunogenicity, Vaccine
Mice
Models, Animal
multidisciplinary
Mutants
Mutation
Neoantigens
Neoplasms - therapy
Neoplasms - virology
Neutralization
Neutralization Tests
Neutralizing
Papillomaviridae - genetics
Papillomaviridae - immunology
Papillomavirus Infections - therapy
Papillomavirus Infections - virology
Papillomavirus Vaccines - administration & dosage
Papillomavirus Vaccines - genetics
Papillomavirus Vaccines - immunology
Protein Multimerization - genetics
Protein Multimerization - immunology
Science
Science (multidisciplinary)
Self-assembly
Sequences
Stoichiometry
Vaccines
Vaccines, Virus-Like Particle - administration & dosage
Vaccines, Virus-Like Particle - genetics
Vaccines, Virus-Like Particle - immunology
Virus-like particles
Viruses
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Title Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles
URI https://link.springer.com/article/10.1038/s41467-020-16639-1
https://www.ncbi.nlm.nih.gov/pubmed/32503989
https://www.proquest.com/docview/2409865443
https://search.proquest.com/docview/2410368772
https://pubmed.ncbi.nlm.nih.gov/PMC7275066
https://doaj.org/article/a48ad75cb64149f78c08387b5f6a5505
Volume 11
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