Human Papillomavirus T and B Cell Responses

Bonnez, William

Abstract

Genital human papillomavirus (HPV) infections represent the most common viral sexually transmitted disease in the United States. These functions cause conditions that include anogenital warts and cervical dysplasias. These diseases can spontaneously regress but the immunologic mechanisms that contribute to the regression are poorly characterized. The experiments in animal models strongly suggest that papillomavirus-associated diseases can be prevented by immunization with virus-like particles (VLP) derived from the major capsid protein of HPV. The present proposal will focus on clinical samples from two unique patient populations. The first is comprised of human volunteers vaccinated with the first HPV type 11 VLP vaccine. This trial is completed and lymphocytes and sera are available. A second group with clinically evident anogenital warts will be treated with autogenous vaccination to induce clinical regression. Sera, peripheral blood mononuclear cells, and most importantly, wart infiltrating lymphocytes will be available for study. These samples will be utilized to study the antigen specificity of the B and T cell populations involved in HPV- specific vaccine responses and anogenital wart regression. Specifically, the peripheral T cells responses to structural and non-structural HPV-6 and -11 proteins will be identified, and the fine specificity for the reactive proteins will be further determined. The frequency of these HPV-6 and-11 specific CD4 and CD 8 T cells will be measured in peripheral blood. Using these results as a guide, the antigenic specificity and frequency of infiltrating T lymphocytes in anogenital warts will be determined. The specific relationship between disease regression and T cell populations will be investigated. For the B cells, the capsid protein conformational and linear epitopes that are recognized by the subjects will be determined, and whether any of the linear epitopes are neutralizing will be established.