Immunoprotective effect of an in silico designed multiepitope cancer vaccine with BORIS cancer-testis antigen target in a murine mammary carcinoma model

• Published in: Scientific reports Vol. 11; no. 1; p. 23121
• Main Authors: Mahdevar, Elham, Kefayat, Amirhosein, Safavi, Ashkan, Behnia, Amirhossein, Hejazi, Seyed Hossein, Javid, Amaneh, Ghahremani, Fatemeh
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30-11-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/590; 631/67/1347; 631/67/322; 631/67/580; Animals; Antigens; Breast cancer; Cancer; Cancer vaccines; Cancer Vaccines - chemistry; Cancer Vaccines - immunology; Carcinoma; Cell Line; Cell Line, Tumor; Cell Proliferation; Chromatography, Liquid; Computational Biology; Computer Simulation; Cytotoxicity; Deoxyribonucleic acid; Disease Models, Animal; DNA; DNA vaccines; DNA-Binding Proteins - biosynthesis; E coli; Epitopes; Female; Humanities and Social Sciences; Immune response; Immunity, Humoral; Immunization; Immunodominance; Immunogenicity; Immunoglobulin G; Immunotherapy; Interferon-gamma - chemistry; Interleukin 4; Liquid chromatography; Lymphocytes; Lymphocytes T; Mammary gland; Mammary Neoplasms, Animal - immunology; Mammary Neoplasms, Animal - prevention & control; Mammary Neoplasms, Animal - therapy; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - prevention & control; Mammary Neoplasms, Experimental - therapy; Metastases; Metastasis; Mice; Mice, Inbred BALB C; multidisciplinary; Neoplasm Metastasis; Nucleotide sequence; Proteins; Science; Science (multidisciplinary); Serum levels; Splenocytes; T-Lymphocytes, Cytotoxic - immunology; Tumors; Vaccines; Vaccines, Subunit; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-01770-w

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.