In silico design and evaluation of a novel mRNA vaccine against BK virus: a reverse vaccinology approach

• Published in: Immunologic research 2023-06, Vol.71 (3), p.422-441
• Main Authors: Mohammadi, Yasaman, Nezafat, Navid, Negahdaripour, Manica, Eskandari, Sedigheh, Zamani, Mozhdeh
• Format: Article
• Language: English
• Subjects: Allergenicity; Allergology; Antigenicity; Antigens; Antiviral agents; Biomedical and Life Sciences; Biomedicine; BK Virus - genetics; Comorbidity; Computational Biology; Design; Epitopes; Epitopes, B-Lymphocyte - genetics; Epitopes, T-Lymphocyte - genetics; Gene expression; Graft rejection; Human populations; Humans; Immune clearance; Immune response; Immunogenicity; Immunology; Immunosuppression; Internal Medicine; Kidney transplantation; Kidney Transplantation - adverse effects; Lymphocytes; Lymphocytes B; Malignancy; Medicine/Public Health; Molecular Docking Simulation; Molecular dynamics; mRNA; mRNA Vaccines; Nephropathy; Optimization; Original; Original Article; Pathogens; Polyomavirus Infections - epidemiology; Polyomavirus Infections - etiology; Population studies; RNA, Messenger - genetics; Simulation; TLR4 protein; Toll-like receptors; Toxicity; Vaccines; Vaccinology - methods; Viruses; World population
• ISSN: 0257-277X; 1559-0755; 1559-0755
• DOI: 10.1007/s12026-022-09351-3

Human polyomavirus type 1, or BK virus (BKV), is a ubiquitous pathogen belonging to the polyomaviridae family mostly known for causing BKV-associated nephropathy (BKVN) and allograft rejection in kidney transplant recipients (KTRs) following the immunosuppression regimens recommended in these patients. Reduction of the immunosuppression level and anti-viral agents are the usual approaches for BKV clearance, which have not met a desired outcome yet. There are also debating matters such as the effect of this pathogen on emerging various comorbidities and the related malignancies in the human population. In this study, a reverse vaccinology approach was implemented to design a mRNA vaccine against BKV by identifying the most antigenic proteins of this pathogen. Potential immunogenic T and B lymphocyte epitopes were predicted through various immunoinformatic tools. The final epitopes were selected according to antigenicity, toxicity, allergenicity, and cytokine inducibility scores. According to the obtained results, the designed vaccine was antigenic, neutral at the physiological pH, non-toxic, and non-allergenic with a world population coverage of 93.77%. Since the mRNA codon optimization ensures the efficient expression of the vaccine in a host cell, evaluation of different parameters showed our designed mRNA vaccine has a stable structure. Moreover, it had strong interactions with toll-like receptor 4 (TLR4) according to the molecular dynamic simulation studies. The in silico immune simulation analyses revealed an overall increase in the immune responses following repeated exposure to the designed vaccine. Based on our findings, the vaccine candidate is ready to be tested as a promising novel mRNA therapeutic vaccine against BKV.