title: Immunological analyses of human papillomavirus capsids.
abstract: Recombinant human papillomavirus (HPV) virus-like particles (VLPs) are promising vaccine candidates for controlling anogenital HPV disease. Questions remain, however, concerning the extent of capsid antigenic similarity between closely related virus genotypes. To investigate this issue, we produced VLPs and corresponding polyclonal immune sera from several anogenital HPV types, and examined these reagents in enzyme-linked immunosorbent assays (ELISAs) and in cross-neutralization studies. Despite varying degrees of L1 genetic sequence relatedness, VLPs of each type examined induced high-titer serum polyclonal antibody responses that were entirely genotype-specific. In an in vitro infectivity assay, only cognate VLP antisera were able to neutralize pseudovirions of HPV-16, HPV-18 and HPV-33, with two exceptions: HPV-31 and HPV-45 VLP post-immune sera demonstrated low levels of neutralizing activity against pseudovirions of HPV-33 and HPV-18, respectively. In other experiments, epitopes shared between closely related types were found to be less immunogenic than, and antigenically distinct from, primary type-specific B-cell determinants of the viral capsid. In addition, results from epitope blocking experiments suggested a close correlation between primary type-specific capsid antigenic sites and virion neutralization. These findings support the view that papillomavirus genotypes denote unique viral serotypes, and suggest that a successful vaccine for these viruses will likely require the inclusion of VLPs of each serotype for which protection is desired.
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Mainz, D-55101, Mainz, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Giroglou
authors.forename: M
authors.initials: M
authors.lastname: Sapp
authors.forename: C
authors.initials: C
authors.lastname: Lane
authors.forename: C
authors.initials: C
authors.lastname: Fligge
authors.forename: N D
authors.initials: ND
authors.lastname: Christensen
authors.forename: R E
authors.initials: RE
authors.lastname: Streeck
authors.forename: R C
authors.initials: RC
authors.lastname: Rose
mesh_terms: D000042:Absorption; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D002213:Capsid / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005838:Genotype; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D009500:Neutralization Tests; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D011487:Protein Conformation; D011489:Protein Denaturation; D012703:Serotyping; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D007106:Immune Sera; D014614:Vaccines, Synthetic; D014765:Viral Vaccines