Cell-mediated immune response is thought to play an important role in controlling human papillomavirus (HPV) infections. The identification of HPV antigens targeted by the immune response that are involved in the regression of HPV-induced diseases may be useful in future peptide-based therapeutic vaccines. The overall goal of this work was to find immune responses associated with clinical resolution of HPV-induced common warts (Chapter 1) and cervical dysplasia (Chapter 2). The main objectives of the first study were to assess the safety of Candin®, a brand of Candida antigen used as a treatment of common warts, and to examine HPV-specific T-cell responses. None of the 18 patients experienced adverse events higher than Grade 2 (moderate). Six (60%) of 10 patients examined (9 of whom were responders to treatment) had a positive response to HPV-57 L1-peptide (380-412). The detection of positive immune responses to L1-peptide in 6 (67%) of 9 patients responding to treatment suggests that HPV-57 L1-specific T-cells may play a role in wart regression. In the second study, the objectives were to compare HPV-specific CD4+ T-cell responses and frequencies of regulatory T-cells (Tregs) between patients whose cervical disease regressed and those whose cervical disease persisted. The detection of CD4+ T-cell immune response to HPV-16 E6 antigens in the regressor group (45.5%) was significantly higher than in the persistor group (19.6%) (p=.015) but not to E7 antigens (19.6% vs. 5.9%; p=.25), suggesting that CD4+ T-cell immune response to HPV-16 E6 protein is associated with natural regression of cervical lesions. There was no difference in the mean percentage of CD4+CD25+Foxp3+ Tregs in CD4+ T-cell population between regressors (3.01%; SE 0.21%; n=30) and persistors (2.96%; 0.15%; n=45). The first study revealed the potential of Candida antigen as a CD4+ T-helper-1 cytokine promoting agent possibly suitable to be used as a vaccine adjuvant. The second study demonstrated the importance of CD4+ T-cell responses to E6 antigens in cervical disease regression. In the near future, our group will investigate the safety and efficacy of a therapeutic vaccine that incorporates HPV-16 E6 antigens with Candin as an adjuvant.
|Commitee:||Cannon, Martin, Gray, Wayne, Williams, D. Keith, van Rhee, Frits|
|School:||University of Arkansas for Medical Sciences|
|Department:||Interdisciplinary Biomedical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 72/04, Dissertation Abstracts International|
|Keywords:||Cell-mediated immune response, Cervical intraepithelial neoplasia, Common warts, HPV|
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