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Human Papilloma Virus (HPV) Immunology Laboratory

Research

Our research efforts are directed toward a better characterization of the cellular immune response to HPV in studies of the natural history of cervical cancer and HPV vaccines. Cervical cancer is the second most common cancer diagnosed among women worldwide with approximately 500,000 new cases and over 200,000 deaths per year. Genital HPV infections have been found to be the central etiological risk factor for cervical cancer and are the most common viral sexually transmitted diseases worldwide. Thererfore, the development of a prophylactic vaccine against HPV-16 and possibly other known oncogenic HPV types is needed to decrease the incidence of cervical cancer.

Our laboratory is involved in examining cellular immune responses to HPV antigens (E2, E6 and E7) in natural history studies of HPV infection, with the goal of identifying putative correlates of immune protection against infection and disease progression. We are also investigating immune responses to HPV-like particles (VLPs), composed of the L1 capsid protein, which are a promising vaccine candidate currently in clinical trials. Responses are evaluated using proliferation, cytokine profiling and/or T cell cytotoxicity assays. In Phase I and II clinical trials, VLPs have been found to safely induce a strong humoral response even when administered in the absence of an adjuvant. Vaccination with HPV-16 L1 VLP has shown excellent protection against persistent infection.

In immunogenicity studies, we have shown that vaccination with HPV-16 L1 VLP induces L1-specific T cell responses detectable by proliferation of both CD4+ and CD8+ T cells and in vitro production of both Th1, Th2 and inflammatory cytokines. Although protection afforded by vaccination with the HPV-16 L1 VLP vaccine is attributed to neutralizing antibodies, it is known that cellular immunity responses are necessary for efficacious and sustained humoral responses. Thus, the precise mechanisms of protection as well as the specific types of responses required for long-term protection are poorly understood. We are interested in understanding the role of cell-mediated immune responses in prophylactic and therapeutic vaccines, with the aim of identifying putative biomarkers of protection against infection or disease. The laboratory is also interested in the development and validation of immunologic methods applicable to field studies, which include whole blood assays for multiplex cytokine detection, preparation of samples in remote sites for flow cytometric analysis and development of methods for cervical immunity analysis.