Implementation of Vaccinomics and In-Silico Approaches to Construct Multimeric Based Vaccine Against Ovarian Cancer

Muhammad Sufyan; Farah Shahid; Faiza Irshad; Anam Javaid; Muhammad Qasim; Usman Ali Ashfaq

doi:10.1007/s10989-021-10294-w

Implementation of Vaccinomics and In-Silico Approaches to Construct Multimeric Based Vaccine Against Ovarian Cancer

Int J Pept Res Ther. 2021;27(4):2845-2859. doi: 10.1007/s10989-021-10294-w. Epub 2021 Oct 19.

Authors

Muhammad Sufyan¹, Farah Shahid¹, Faiza Irshad², Anam Javaid¹, Muhammad Qasim¹, Usman Ali Ashfaq¹

Affiliations

¹ Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.
² Environment Biotechnology Lab, Institute of Botany, University of the Punjab, Lahore, Pakistan.

Abstract

One of the most common gynecologic cancers is ovarian cancer and ranked third after the other two most common cancers: cervical and uterine. The highest mortality rate has been observed in the case of ovarian cancer. To treat ovarian cancer, an immune-informatics approach was used to design a multi-epitope vaccine (MEV) structure. Epitopes prediction of the cancer testis antigens (NY-ESO-1), A-Kinase anchor protein (AKAP4), Acrosin binding protein (ACRBP), Piwi-like protein (PIWIL3), and cancer testis antigen 2 (LAGE-1) was done. Non-toxic, highly antigenic, non-allergenic, and overlapping epitopes were shortlisted for vaccine construction. Chosen T-cell epitopes displayed a robust binding attraction with their corresponding Human Leukocyte Antigen (HLA) alleles demonstrated 97.59% of population coverage. The vaccine peptide was established by uniting three key constituents, comprising the 14 epitopes of CD8 + cytotoxic T lymphocytes (CTLs), 5 helper epitopes, and the adjuvant. For the generation of the effective response of CD4 + cells towards the T-helper cells, granulocyte-macrophage-colony-stimulating factor (GM-CSF) was applied. With the addition of adjuvants and linkers, the construct size was 547 amino acids. The developed MEV structure was predicted to be antigenic, non-toxic, non-allergenic, and firm in nature. I-tasser anticipated the 3D construction of MEV. Moreover, disulfide engineering further enhanced the stability of the final vaccine protein. In-silico cloning and vaccine codon optimization were done to analyze the up-regulation of its expression. The outcomes established the vaccine's immunogenicity and safety profile, besides its aptitude to encourage both humoral and cellular immune responses. The offered vaccine, grounded on our in-silico investigation, may be considered for ovarian cancer immunotherapy.

Supplementary information: The online version contains supplementary material available at 10.1007/s10989-021-10294-w.

Keywords: GM-CSF; Human leukocyte antigen; Immunotherapy; MEV; Ovarian cancer.