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      A Protective and Broadly Cross-Neutralizing Epitope of Human Papillomavirus L2

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          ABSTRACT

          We generated a monoclonal antibody, RG-1, that binds to highly conserved L2 residues 17 to 36 and neutralizes human papillomavirus 16 (HPV16) and HPV18. Passive immunotherapy with RG-1 was protective in mice. Antiserum to the HPV16 L2 peptide comprising residues 17 to 36 (peptide 17-36) neutralized pseudoviruses HPV5, HPV6, HPV16, HPV 18, HPV31, HPV 45, HPV 52, HPV 58, bovine papillomavirus 1, and HPV11 native virions. Depletion of HPV16 L2 peptide 17-36-reactive antibodies from cross-neutralizing rabbit and human L2-specific sera abolished cross-neutralization and drastically reduced neutralization of the cognate type. This cross-neutralization of diverse HPVs associated with cervical cancer, genital warts, and epidermodysplasia verruciformis suggests the possibility of a broadly protective, peptide-based vaccine.

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          How will HPV vaccines affect cervical cancer?

          Cancer of the uterine cervix is the second largest cause of cancer deaths in women, and its toll is greatest in populations that lack screening programmes to detect precursor lesions. Persistent infection with 'high risk' genotypes of human papillomavirus (HPV) is necessary, although not sufficient, to cause cervical carcinoma. Therefore, HPV vaccination provides an opportunity to profoundly affect cervical cancer incidence worldwide. A recently licensed HPV subunit vaccine protects women from a high proportion of precursor lesions of cervical carcinoma and most genital warts. Here we examine the ramifications and remaining questions that surround preventive HPV vaccines.
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            Minor capsid protein of human genital papillomaviruses contains subdominant, cross-neutralizing epitopes.

            Vaccination with virus-like particles (VLP), comprising both L1 and L2 of human papillomavirus (HPV) genital types 6, 16, and 18, induces predominantly type-specific neutralizing antibodies. L2 polypeptide vaccines protect animals against experimental challenge with homologous papillomavirus and cross-reactive epitopes are present in HPV L2. To assess L2-specific cross-neutralization of HPV genotypes, sheep were immunized with purified, bacterially expressed HPV6, 16, or 18 L2. In addition to neutralizing the homologous HPV type in vitro, antisera to each HPV L2 also cross-neutralized both heterologous HPV types. This suggests that unlike VLP-based prophylactic HPV vaccines, an L2 polypeptide vaccine may provide broad-spectrum protection. Copyright 2000 Academic Press.
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              Cross-neutralization of cutaneous and mucosal Papillomavirus types with anti-sera to the amino terminus of L2.

              Vaccination with papillomavirus L2 has been shown to induce neutralizing antibodies that protect against homologous type infection and cross-neutralize a limited number of genital HPVs. Surprisingly, we found that antibodies to bovine papillomavirus (BPV1) L2 amino acids 1-88 induced similar titers of neutralizing antibodies against Human papillomavirus (HPV)16 and 18 and BPV1 pseudoviruses and also neutralized HPV11 native virions. These antibodies also neutralized each of the other pseudovirus types tested, HPV31, HPV6 and Cottontail rabbit papillomavirus (CRPV) pseudoviruses, albeit with lower titers. HPV16, HPV18, HPV31, HPV6 and CRPV L2 anti-sera also displayed some cross-neutralization, but the titers were lower and did not encompass all pseudoviruses tested. This study demonstrates the presence of broadly cross-neutralizing epitopes at the N-terminus of L2 that are shared by cutaneous and mucosal types and by types that infect divergent species. BPV1 L2 was exceptionally effective at inducing cross-neutralizing antibodies to these shared epitopes.
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                Author and article information

                Journal
                Journal of Virology
                JVI
                American Society for Microbiology
                0022-538X
                1098-5514
                December 15 2007
                December 15 2007
                October 10 2007
                : 81
                : 24
                : 13927-13931
                Affiliations
                [1 ] Departments of Pathology
                [2 ] Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892-4263
                [3 ] Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania
                [4 ] Oncology
                [5 ] Gynecology & Obstetrics, The Johns Hopkins University, Baltimore, Maryland 21231
                Article
                10.1128/JVI.00936-07
                2168823
                17928339
                ae4503e6-e423-4f79-8b36-a31e4f4f1139
                © 2007
                History

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