Characterization of Human Papillomavirus Type 11-specific Immune Responses in a Preclinical Model

Laryngoscope. 2010 Mar;120(3):504-10. doi: 10.1002/lary.20745.

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-gamma-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 E6(aa44-51) peptide. We determined that the epitope is presented by the MHC class I H2-K(b) 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 E6(aa44-51) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Disease Models, Animal
  • Flow Cytometry
  • Human papillomavirus 11 / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Major Histocompatibility Complex / immunology
  • Mice
  • Mice, Inbred C57BL
  • Papillomavirus Infections / immunology*
  • Vaccines, DNA / immunology*

Substances

  • Vaccines, DNA
  • Interferon-gamma