title: Immunization with a consensus epitope from human papillomavirus L2 induces antibodies that are broadly neutralizing.
abstract: Vaccines targeting conserved epitopes in the HPV minor capsid protein, L2, can elicit antibodies that can protect against a broad spectrum of HPV types that are associated with cervical cancer and other HPV malignancies. Thus, L2 vaccines have been explored as alternatives to the current HPV vaccines, which are largely type-specific. In this study we assessed the immunogenicity of peptides spanning the N-terminal domain of L2 linked to the surface of a highly immunogenic bacteriophage virus-like particle (VLP) platform. Although all of the HPV16 L2 peptide-displaying VLPs elicited high-titer anti-peptide antibody responses, only a subset of the immunogens elicited antibody responses that were strongly protective from HPV16 pseudovirus (PsV) infection in a mouse genital challenge model. One of these peptides, mapping to HPV16 L2 amino acids 65-85, strongly neutralized HPV16 PsV but showed little ability to cross-neutralize other high-risk HPV types. In an attempt to broaden the protection generated through vaccination with this peptide, we immunized mice with VLPs displaying a peptide that represented a consensus sequence from high-risk and other HPV types. Vaccinated mice produced antibodies with broad, high-titer neutralizing activity against all of the HPV types that we tested. Therefore, immunization with virus-like particles displaying a consensus HPV sequence is an effective method to broaden neutralizing antibody responses against a type-specific epitope.
authors: Department of Molecular Genetics and Microbiology, University of New Mexico, MSC08-4660, Albuquerque, NM 87131, United States.
authors: Mitchell
authors: M
authors: Tyler
authors: Department of Molecular Genetics and Microbiology, University of New Mexico, MSC08-4660, Albuquerque, NM 87131, United States.
authors: Ebenezer
authors: E
authors: Tumban
authors: Department of Molecular Genetics and Microbiology, University of New Mexico, MSC08-4660, Albuquerque, NM 87131, United States.
authors: Agnieszka
authors: A
authors: Dziduszko
authors: Department of Molecular Genetics and Microbiology, University of New Mexico, MSC08-4660, Albuquerque, NM 87131, United States.
authors: Michelle A
authors: MA
authors: Ozbun
authors: Department of Molecular Genetics and Microbiology, University of New Mexico, MSC08-4660, Albuquerque, NM 87131, United States.
authors: David S
authors: DS
authors: Peabody
authors: Department of Molecular Genetics and Microbiology, University of New Mexico, MSC08-4660, Albuquerque, NM 87131, United States. Electronic address: bchackerian@salud.unm.edu.
authors: Bryce
authors: B
authors: Chackerian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D036022:Capsid Proteins / Q000276:immunology*; D016384:Consensus Sequence; D056738:Cross Protection; D000939:Epitopes / Q000276:immunology*; D005260:Female; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D058425:Vaccines, Virus-Like Particle
keywords: HPV vaccine; L2; Neutralizing epitope; Virus-like particles