title: A papillomavirus-like particle (VLP) vaccine displaying HPV16 L2 epitopes induces cross-neutralizing antibodies to HPV11.
abstract: Peptides of the papillomavirus L2 minor capsid protein can induce antibodies (Ab) that neutralize a broad range of human papillomavirus (HPV) genotypes. Unfortunately, L2 is antigenically subdominant to L1 in the virus capsid. To induce a strong anti-L2 Ab response with cross-neutralizing activity to other mucosal types, chimeric virus-like particles (VLP) were generated in which HPV16 L2 neutralization epitopes (comprising L2 residues 69-81 or 108-120) are inserted within an immunodominant surface loop (between residues 133 and 134) of the L1 major capsid protein of bovine papillomavirus type 1 (BPV1). These chimeras self-assembled into pentameric capsomers, or complete VLP similar to wild type (wt) L1 protein. Immunization of rabbits with assembled particle preparations induced L2-specific serum Ab with titers 10-fold higher than those induced by cognate synthetic L2 peptides coupled to KLH. Antisera to both chimeric proteins partially neutralized HPV16 pseudovirions, confirming that both HPV16 L2 peptides define neutralization epitopes. When analyzed for the ability to cross-neutralize infection by authentic HPV11 virions, using detection of early viral RNA by RT-PCR-assays as the readout, immune serum to chimeric protein comprising L2 residues 69-81, but not 108-120, was partially neutralizing. In addition, mouse-antiserum induced by vaccinations with synthetic L2 peptide 108-120, but not 69-81, was partially neutralizing in this assay. Induction of cross-neutralization Ab by L2 epitopes displayed on chimeric VLP represents a possible strategy for the generation of broad-spectrum vaccines to protect against relevant mucosal HPV and associated neoplasia.
authors.affiliation: Laboratory of Viral Oncology, Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Slupetzky
authors.forename: Ratish
authors.initials: R
authors.lastname: Gambhira
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Culp
authors.forename: Saeed
authors.initials: S
authors.lastname: Shafti-Keramat
authors.forename: Christina
authors.initials: C
authors.lastname: Schellenbacher
authors.forename: Neil D
authors.initials: ND
authors.lastname: Christensen
authors.forename: Richard B S
authors.initials: RB
authors.lastname: Roden
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kirnbauer
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D052688:Bovine papillomavirus 1 / Q000235:genetics; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D052140:Human papillomavirus 11 / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D051379:Mice; D023421:Models, Animal; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D022721:Vaccines, Virosome / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D022721:Vaccines, Virosome