Molecular Analysis of Papillomavirus Immunity

Human papillomavirus (HPV) infection causes hyperproliferative lesions in cutaneous and mucosal epithelium. More than 80 different HPV types have been identified and 2/3 of these have been detected in anogenital sites. These latter HPV infections are spread by sexual contact, and several HPV types have been associated with malignant progression. HPV-associated cervical cancers are the second leading cause of death in women world-wide.

Host immunity plays a significant role in determining the outcome of infection by papillomaviruses. A successful immune response leads to regression of lesions and protection against reinfection. An ineffective and/or anergic response may result in persistent lesions which have increased risk of malignant progression, especially for some papillomavirus types. Characterization of the viral epitopes that trigger immunity to papillomavirus infection therefore will be key to planning immunotherapeutic management of this infectious disease.

The overall research theme in our laboratory is studies on immunity to papillomavirus infections. The major subprojects include: (i) characterization of viral capsid neutralization epitopes; (ii) vaccine development; (iii) analysis of T-cell recognition of viral epitopes on virus-infected papilloma cells; (iv) papillomavirus animal model systems; (v) model systems to test for anti-viral compounds; and (vi) methods to propagate human papillomaviruses. Our research is currently centered on the analysis of papillomavirus capsid epitopes recognized by panels of neutralizing monoclonal antibodies. Epitope mapping utilizes papillomavirus virus-like particles (VLPs) that are prepared in insect cells using recombinant baculoviruses. We also have two rabbit papillomavirus model systems that are being used to dissect the T-cell responses to papillomas, and to determine which early viral genes that are expressed in papilloma cells are the targets of cell-mediated immunity leading to papilloma regressions. In addition, we are using the rabbit papillomavirus models for the testing of protective and prophylactic vaccines.