Antitumor Response to a Codon-Optimized HPV-16 E7/HSP70 Fusion Antigen DNA Vaccine

Iran J Immunol. 2017 Sep;14(3):180-191.

Abstract

Background: Vaccines based on virus-like particles are effective against Human Papilloma Virus (HPV) infection; however, they have not shown a therapeutic effect against HPV-associated diseases. New immunotherapy strategies based on immune responses against tumor antigens can positively affect the clearance of HPV-associated lesions.

Objective: To generate two therapeutic fusion DNA vaccines (optimizedE7/mouseHSP70 and wildE7/mouseHSP70) to induce antitumor specific responses in mice models.

Methods: Mice were immunized with recombinant DNA vaccines. The splenocytes of immunized mice were collected and lactate dehydrogenase and IFN-γ productions were measured after three injections in order to evaluate cytotoxic T lymphocytes (CTLs) activity. MTT assay was carried out for lymphocyte stimulation.

Results: The fusion DNA vaccines, specifically uE7-HSP70, elicited varying levels of IFN-γ and CTLs responses compared to the control group (P<0.05). Furthermore, antitumor response and tumor size reduction in fusion DNA vaccines groups were significantly higher than in the negative control group (P<0.05).

Conclusion: It is concluded that our fusion DNA vaccines considerably enhanced specific cellular responses against HPV tumor model. In addition, optimized E7 showed a notable immunogenicity and inhibitory effect on the reduction of tumor size.

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Cancer Vaccines / immunology*
  • Codon / genetics
  • Cytotoxicity, Immunologic
  • Female
  • HSP70 Heat-Shock Proteins / genetics
  • Human papillomavirus 16 / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • L-Lactate Dehydrogenase / blood
  • Mice
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus Infections / immunology*
  • Recombinant Fusion Proteins / genetics
  • T-Lymphocytes, Cytotoxic / immunology*
  • Treatment Outcome
  • Tumor Burden
  • Uterine Cervical Neoplasms / immunology*
  • Vaccines, DNA
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*
  • Virion

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Codon
  • HSP70 Heat-Shock Proteins
  • Papillomavirus E7 Proteins
  • Recombinant Fusion Proteins
  • Vaccines, DNA
  • Viral Vaccines
  • oncogene protein E7, Human papillomavirus type 16
  • Interferon-gamma
  • L-Lactate Dehydrogenase