Immunologic responses to a novel DNA vaccine targeting human papillomavirus-11 E6E7

Research output: Contribution to journalArticle

Abstract

Objectives/Hypothesis: Recurrent respiratory papillomatosis (RRP) is a benign disease caused by human papillomavirus (HPV) types 6 and 11. Although a prophylactic vaccine against RRP is available, a therapeutic vaccine is needed to treat those already infected. The objective of our study was to design and test a DNA vaccine targeting HPV11 proteins. Study Design: Preclinical scientific investigation. Methods: A DNA vaccine encoding the HPV11 E6 and E7 genes linked to calreticulin (CRT) was generated. Immunologic response to the HPV11 CRT/E6E7 vaccine was measured by vaccinating C57BL/6 mice via electroporation and measuring CD8+T cell responses from harvested splenocytes. A tumor cell line containing HPV11-E6E7 was created, and the ability of novel DNA vaccine to control tumor growth was measured in vivo. Results: Our vaccine generated a significant and specific CD8+T-cell response against the HPV11-E6aa41-70 peptide. The CD8+T-cell responses did not recognize E7 epitopes, indicating E6 immunodominance. CD8+responses were augmented in the CRT-linked vaccine compared to a control non-CRT vaccine. The HPV11 CRT/E6E7 vaccine was used to treat mice inoculated with a HPV11 E6E7 expressing tumor cell line after temporary CD3 depletion to facilitate tumor growth. Vaccinated mice had a significantly lower tumor growth rate (P=.029) and smaller tumor volumes compared to control mice, indicating an augmented immunologic response in vaccinated mice. Conclusions: A DNA vaccine targeting HPV11 E6E7 generates a specific HPV11 CD-8+T-cell response capable of reducing the growth of HPV11-expressing tumors. DNA vaccines are a promising immunologic strategy for treating RRP.

Original languageEnglish (US)
JournalLaryngoscope
DOIs
StateAccepted/In press - 2017

Keywords

  • DNA vaccines
  • HPV11
  • Human papillomavirus
  • Laryngeal papilloma
  • Recurrent respiratory papillomatosis

ASJC Scopus subject areas

  • Otorhinolaryngology

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