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Immunoprotective Effect of an in Silico Designed Multiepitope Cancer Vaccine With Boris Cancer-Testis Antigen Target in a Murine Mammary Carcinoma Model Publisher Pubmed



Mahdevar E1 ; Kefayat A2 ; Safavi A3 ; Behnia A4 ; Hejazi SH5 ; Javid A1 ; Ghahremani F6
Authors
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Authors Affiliations
  1. 1. Department of Biological Sciences, Faculty of Science and Engineering, Science and Arts University, Yazd, Iran
  2. 2. Department of Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
  4. 4. Department of Biology, Faculty of the Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
  5. 5. Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  6. 6. Department of Medical Physics and Radiotherapy, School of Paramedicine, Arak University of Medical Sciences, Arak, Iran

Source: Scientific Reports Published:2021


Abstract

In our previous study, immunoinformatic tools were used to design a novel multiepitope cancer vaccine based on the most immunodominant regions of BORIS cancer-testis antigen. The final vaccine construct was an immunogenic, non-allergenic, and stable protein consisted of multiple cytotoxic T lymphocytes epitopes, IFN-γ inducing epitopes, and B cell epitopes according to bioinformatic analyzes. Herein, the DNA sequence of the final vaccine construct was placed into the pcDNA3.1 vector as a DNA vaccine (pcDNA3.1-VAC). Also, the recombinant multiepitope peptide vaccine (MPV) was produced by a transfected BL21 E. coli strain using a recombinant pET-28a vector and then, purified and screened by Fast protein liquid chromatography technique (FPLC) and Western blot, respectively. The anti-tumor effects of prophylactic co-immunization with these DNA and protein cancer vaccines were evaluated in the metastatic non-immunogenic 4T1 mammary carcinoma in BALB/c mice. Co-immunization with the pcDNA3.1-VAC and MPV significantly (P < 0.001) increased the serum levels of the MPV-specific IgG total, IgG2a, and IgG1. The splenocytes of co-immunized mice exhibited a significantly higher efficacy to produce interleukin-4 and interferon-γ and proliferation in response to MPV in comparison with the control. The prophylactic co-immunization regime caused significant breast tumors’ growth inhibition, tumors’ weight decrease, inhibition of metastasis formation, and enlarging tumor-bearing mice survival time, without any considerable side effects. Taking together, this cancer vaccine can evoke strong immune response against breast tumor and inhibits its growth and metastasis. © 2021, The Author(s).
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