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

• Published in: Biotechnology letters 2021-09, Vol.43 (9), p.1933-1944
• Main Authors: Mousavi, Tahoora, Valadan, Reza, Rafiei, Alireza, Abbasi, Ali, Haghshenas, Mohammad Reza
• Format: Article
• Language: English
• Subjects: Alphapapillomavirus - genetics; Alphapapillomavirus - immunology; Alphapapillomavirus - metabolism; Animal models; Animals; Antibodies; Antibody response; Applied Microbiology; Assaying; Biochemistry; Biocompatibility; Biomedical and Life Sciences; Biotechnology; Cancer; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Cancer Vaccines - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cervix; Cloning, Molecular; Cytokines; Cytotoxicity; E coli; E7 protein; Escherichia coli - genetics; Escherichia coli - growth & development; Female; Fusion protein; HIV; HIV-1 - genetics; HIV-1 - metabolism; Human immunodeficiency virus; Human papillomavirus; 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; Immunogenicity; Immunotherapy; Interleukin 4; Life Sciences; Lung Neoplasms - prevention & control; Lung Neoplasms - virology; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred C57BL; Microbiology; Original Research Paper; Oropharyngeal cancer; 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; Proteins; Public health; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - metabolism; Survival; tat Gene Products, Human Immunodeficiency Virus - genetics; Tat protein; Toxicity; Tumors; Vaccination; Vaccines; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; Vaccines, Synthetic - metabolism; Western blotting; γ-Interferon
• ISSN: 0141-5492; 1573-6776
• DOI: 10.1007/s10529-021-03166-2

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.