title: Functional assessment and structural basis of antibody binding to human papillomavirus capsid.
abstract: Persistent high-risk human papillomavirus (HPV) infection is linked to cervical cancer. Two prophylactic virus-like particle (VLP)-based vaccines have been marketed globally for nearly a decade. Here, we review the HPV pseudovirion (PsV)-based assays for the functional assessment of the HPV neutralizing antibodies and the structural basis for these clinically relevant epitopes. The PsV-based neutralization assay was developed to evaluate the efficacy of neutralization antibodies in sera elicited by vaccination or natural infection or to assess the functional characteristics of monoclonal antibodies. Different antibody binding modes were observed when an antibody was complexed with virions, PsVs or VLPs. The neutralizing epitopes are localized on surface loops of the L1 capsid protein, at various locations on the capsomere. Different neutralization antibodies exert their neutralizing function via different mechanisms. Some antibodies neutralize the virions by inducing conformational changes in the viral capsid, which can result in concealing the binding site for a cellular receptor like 1A1D-2 against dengue virus, or inducing premature genome release like E18 against enterovirus 71. Higher-resolution details on the epitope composition of HPV neutralizing antibodies would shed light on the structural basis of the highly efficacious vaccines and aid the design of next generation vaccines. In-depth understanding of epitope composition would ensure the development of function-indicating assays for the comparability exercise to support process improvement or process scale up. Elucidation of the structural elements of the type-specific epitopes would enable rational design of cross-type neutralization via epitope re-engineering or epitope grafting in hybrid VLPs.
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian, China.|School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian, China.|School of Public Health, Xiamen University, Xiamen, Fujian, China.|School of Life Science, Xiamen University, Xiamen, Fujian, China.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Yorgo
authors.initials: Y
authors.lastname: Modis
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian, China.|School of Life Science, Xiamen University, Xiamen, Fujian, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian, China.|School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian, China.|School of Public Health, Xiamen University, Xiamen, Fujian, China.|School of Life Science, Xiamen University, Xiamen, Fujian, China.
authors.forename: Ningshao
authors.initials: N
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian, China.|School of Public Health, Xiamen University, Xiamen, Fujian, China.
authors.forename: Qinjian
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000821:virology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes