Induction of antitumor immunity in vivo following delivery of a novel HPV-16 DNA vaccine encoding an E6/E7 fusion antigen

Vaccine. 2009 Jan 14;27(3):431-40. doi: 10.1016/j.vaccine.2008.10.078. Epub 2008 Nov 18.

Abstract

Human papillomavirus type 16 (HPV-16) infection is associated with a majority of cervical cancers and a significant proportion of head and neck cancers. Here, we describe a novel-engineered DNA vaccine that encodes a HPV-16 consensus E6/E7 fusion gene (pConE6E7) with the goal of increasing its antitumor cellular immunity. Compared to an early stage HPV-16 E7 DNA vaccine (pE7), this construct was up to five times more potent in driving E7-specific cellular immune responses. Prophylactic administration of this vaccine resulted in 100% protection against HPV E6 and E7-expressing tumors. Therapeutic studies indicated that vaccination with pConE6E7 prevented or delayed the growth of tumors. Moreover, immunization with pConE6E7 could also partially overcome immune tolerance in E6/E7 transgenic mice. Such DNA immunogens are interesting candidates for further study to investigate mechanisms of tumor immune rejection in vivo.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Base Sequence
  • DNA, Viral / chemistry
  • DNA, Viral / genetics
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Neoplasms / pathology
  • Neoplasms / prevention & control
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines / genetics
  • Papillomavirus Vaccines / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Sequence Analysis, DNA
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*

Substances

  • Antigens, Viral
  • DNA, Viral
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Vaccines, DNA
  • oncogene protein E7, Human papillomavirus type 16

Associated data

  • GENBANK/FJ229356