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- Title
Characterization of human papillomavirus type 11-specific immune responses in a preclinical model.
- Authors
Peng, Shiwen; Best, Simon R.; Hung, Chien-Fu; Loyo, Myriam; Lyford-Pike, Sofia; Flint, Paul W.; Tunkel, David E.; Saunders, John R.; Wu, T. C.; Pai, Sara I.
- Abstract
Objectives/Hypothesis: Human papillomavirus (HPV) types 6 and 11 are associated with recurrent respiratory papillomatosis (RRP). Although a prophylactic vaccine has been developed that protects against HPV infection, a therapeutic vaccine is still needed for those patients infected with and/or suffering from persistent disease. Therefore, we developed a novel, therapeutic DNA vaccine targeting HPV-11 and characterized the in vivo immunologic responses generated against HPV-11 E6 and E7 after DNA vaccination in a preclinical model. Methods: We generated a DNA vaccine that encodes the HPV-11 E6 and E7 genes in a pcDNA3 backbone plasmid. We then vaccinated C57BL/6 mice with the pcDNA3-HPV11-E6E7 DNA plasmid. Splenocytes were harvested from these vaccinated animals and were incubated with overlapping peptides spanning either the HPV-11 E6 or E7 protein. The frequency of interferon-γ-releasing CD8+ T cell responses was then analyzed by flow cytometry. Results: Vaccinated mice with the HPV11-E6E7 DNA generated strong CD8+ T cell responses against the E6aa44-51 peptide. We determined that the epitope is presented by the MHC class I H2-Kb molecule. No significant E7 peptide-specific T cell responses were observed. Conclusions: We developed a novel DNA vaccine that targets the E6 gene of HPV-11. Characterization of the immunologic responses elicited by this DNA vaccine reveals that the E6aa44-51 peptide contains the most immunogenic region for the HPV-11 viral type. Knowledge of this specific T cell epitope and generation of a RRP preclinical model will allow for the development and evaluation of novel vaccine strategies targeting the RRP patient population. Laryngoscope, 2010
- Subjects
PAPILLOMAVIRUS diseases; DNA vaccines; IMMUNE response; CLINICAL trials; EPITOPES; HUMAN papillomavirus vaccines; T cells; THERAPEUTICS
- Publication
Laryngoscope, 2010, Vol 120, Issue 3, p504
- ISSN
0023-852X
- Publication type
Article
- DOI
10.1002/lary.20745