A novel recombinant protein vaccine containing the different E7 proteins of the HPV16, 18, 6, 11 E7 linked to the HIV-1 Tat (47-57) improve cytotoxic immune responses

Biotechnol Lett. 2021 Sep;43(9):1933-1944. doi: 10.1007/s10529-021-03166-2. Epub 2021 Jul 27.

Abstract

Objectives: Human papillomavirus infection (HPV) is the most common viral infection which is causes of cervical, penal, vulvar, anal and, oropharyngeal cancer. E7 protein of HPV is a suitable target for induction of T cell responses and controlling HPV-related cancer. The aim of the current study was to designed and evaluated a novel fusion protein containing the different E7 proteins of the HPV 16, 18, 6 and 11, linked to the cell-penetrating peptide HIV-1 Tat 49-57, in order to improve cytotoxic immune responses in in-vitro and in-vivo.

Results: In this study whole sequence of HPV16,18,6,11 E7-Tat (47-57) and HPV16,18,6,11 E7 cloned into the vector and expressed in E. coli (BL21). The purified protein was confirmed by SDS page and western blotting and then injected into the C57BL/6 mice. The efficiency of the fusion protein vaccine was assessed by antibody response assay, cytokine assay (IL-4 and IFN-γ), CD + 8 cytotoxicity assay and tumor challenge experiment. Result showed that fusion proteins containing Adjuvant (IFA,CFA) could express higher titer of antibody. Also, we showed that vaccination with E7-Tat and, E7-Tat-ADJ induced high frequencies of E7-specific CD8 + T cells and CD107a expression as well as IFN-γ level and enhanced long-term survival in the therapeutic animal models.

Conclusion: Our finding suggested that this novel fusion protein vaccine was able to induce therapeutic efficacy and immunogenicity by improving CD8 + T cell in TC-1 tumor bearing mice; so this vaccine may be appreciated for research against HPV and tumor immunotherapies.

Keywords: E7; Fusion protein; HIV1-Tat (47–57); HPV vaccine; Therapeutic immunization.

MeSH terms

  • Alphapapillomavirus / genetics
  • Alphapapillomavirus / immunology
  • Alphapapillomavirus / metabolism*
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology
  • Cancer Vaccines / metabolism
  • Cloning, Molecular
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Female
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • Human papillomavirus 11 / genetics
  • Human papillomavirus 11 / metabolism
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / metabolism
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / metabolism
  • Human papillomavirus 6 / genetics
  • Human papillomavirus 6 / metabolism
  • Humans
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / virology*
  • Mice
  • Mice, Inbred C57BL
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / metabolism*
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines / administration & dosage*
  • Papillomavirus Vaccines / immunology
  • Papillomavirus Vaccines / metabolism
  • Peptide Fragments / genetics*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Vaccination
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / metabolism
  • tat Gene Products, Human Immunodeficiency Virus / genetics*

Substances

  • Cancer Vaccines
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • tat Gene Products, Human Immunodeficiency Virus
  • tat peptide (47-57), Human immunodeficiency virus 1

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