title: A human monoclonal antibody against HPV16 recognizes an immunodominant and neutralizing epitope partially overlapping with that of H16.V5.
abstract: The presence of neutralizing epitopes in human papillomavirus (HPV) L1 virus-like particles (VLPs) is the structural basis of prophylactic vaccines. An anti-HPV16 neutralizing monoclonal antibody (N-mAb) 26D1 was isolated from a memory B cell of a human vaccinee. The pre-binding of heparan sulfate to VLPs inhibited the binding of both N-mAbs to the antigen, indicating that the epitopes are critical for viral cell attachment/entry. Hybrid VLP binding with surface loop swapping between types indicated the essential roles of the DE and FG loops for both 26D1 (DEa in particular) and H16.V5 binding. Specifically, Tyr(135) and Val(141) on the DEa loop were shown to be critical residues for 26D1 binding via site-directed mutagenesis. Partially overlap between the epitopes between 26D1 and H16.V5 was shown using pairwise epitope mapping, and their binding difference is demonstrated to be predominantly in DE loop region. In addition, 26D1 epitope is immunodominant epitope recognized by both antibodies elicited by the authentic virus from infected individuals and polyclonal antibodies from vaccinees. Overall, a partially overlapping but distinct neutralizing epitope from that of H16.V5 was identified using a human N-mAb, shedding lights to the antibody arrays as part of human immune response to vaccination and infection.
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Yangfei
authors.initials: Y
authors.lastname: Xian
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Daning
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Yuanzhi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Xingjian
authors.initials: X
authors.lastname: Bi
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.|Texas Therapeutics Institute, The Brown Foundation of Molecular Medicine, University of Texas Health Science Center at Houston, Houston TX77030, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: An
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Qinjian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University; Xiamen 361105, China.
authors.forename: Ningshao
authors.initials: N
authors.lastname: Xia
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry*; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000737:chemistry*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000821:virology; D036022:Capsid Proteins / Q000737:chemistry / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D006497:Heparan Sulfate / Q000737:chemistry / Q000494:pharmacology; D052162:Human papillomavirus 16 / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000737:chemistry; D007156:Immunologic Memory; D062105:Molecular Docking Simulation; D009154:Mutation; D009500:Neutralization Tests; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D011485:Protein Binding / Q000187:drug effects; D000072417:Protein Domains; D014611:Vaccination; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D036022:Capsid Proteins; D000939:Epitopes; D006497:Heparan Sulfate; D007106:Immune Sera; D053918:Papillomavirus Vaccines; D058425:Vaccines, Virus-Like Particle