title: Human papillomavirus type 6 virus-like particles present overlapping yet distinct conformational epitopes.
abstract: The epitope for a human papillomavirus (HPV) type 6 conformation-dependent, neutralizing monoclonal antibody (mAb) was partially mapped using HPV L1 recombinant virus-like particles (VLPs). The mAb H6.J54 is cross-reactive with the closely related HPV types 6 and 11. By making HPV-6-like amino acid substitutions in the cottontail rabbit papillomavirus (CRPV) major capsid protein L1, we were able to transfer H6.J54 binding activity into a CRPV/HPV-6 hybrid L1 protein. Full binding activity was achieved with only nine amino acid changes and identified a region centred on the HPV-6 residues 49-54. This region has previously been shown to be a critical part of HPV-6 type-specific epitopes. Fine mapping of the region by scanning a series of alanine substitution mutations showed that in HPV-6 VLPs this type-common epitope overlaps HPV-6 type-specific epitopes.
authors.affiliation: Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Cook
authors.affiliation: Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA.
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.affiliation: The Jake Gittlen Cancer Research Institute, Department of Pathology, Penn State University, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Christensen
authors.affiliation: Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Ludmerer
authors.affiliation: Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: McClements
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics; D003429:Cross Reactions; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000939:Epitopes; D014764:Viral Proteins