Immunoinformatic-Based Multi-Epitope Vaccine Design for Co-Infection of Mycobacterium tuberculosis and SARS-CoV-2

Abstract

(1) Background: Many co-infections of Mycobacterium tuberculosis (MTB) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have emerged since the occurrence of the SARS-CoV-2 pandemic. This study aims to design an effective preventive multi-epitope vaccine against the co-infection of MTB and SARS-CoV-2. (2) Methods: The three selected proteins (spike protein, diacylglycerol acyltransferase, and low molecular weight T-cell antigen TB8.4) were predicted using bioinformatics, and 16 epitopes with the highest ranks (10 helper T lymphocyte epitopes, 2 CD8+ T lymphocytes epitopes, and 4 B-cell epitopes) were selected and assembled into the candidate vaccine referred to as S7D5L4. The toxicity, sensitization, stability, solubility, antigenicity, and immunogenicity of the S7D5L4 vaccine were evaluated using bioinformatics tools. Subsequently, toll-like receptor 4 docking simulation and discontinuous B-cell epitope prediction were performed. Immune simulation and codon optimization were carried out using immunoinformatics and molecular biology tools. (3) Results: The S7D5L4 vaccine showed good physical properties, such as solubility, stability, non-sensitization, and non-toxicity. This vaccine had excellent antigenicity and immunogenicity and could successfully simulate immune responses in silico. Furthermore, the normal mode analysis of the S7D5L4 vaccine and toll-like receptor 4 docking simulation demonstrated that the vaccine had docking potential and a stable reaction. (4) Conclusions: The S7D5L4 vaccine designed to fight against the co-infection of MTB and SARS-CoV-2 may be safe and effective. The protective efficacy of this promising vaccine should be further verified using in vitro and in vivo experiments.

PP19128R, a Multiepitope Vaccine Designed to Prevent Latent Tuberculosis Infection, Induced Immune Responses In Silico and In Vitro Assays

“…TLR agonists and helper peptides were not incorporated into the vaccine design to improve the immunogenicity and targeting of the vaccine. CD8 + T cells and B cells have been reported to be important in eliminating and killing MTB [4,8,23,51]. In another previous study, we developed an MEV named HP13138PB against MTB infection in silico and verified its immunological properties in in vitro experiments [49].…”

“…Furthermore, the best model with the highest C-score was selected for optimization using the GalaxyRefine web server (https://galaxy.seoklab.org/cgi-bin/submit.cgi?type=REFINE (accessed on 16 February 2022). Verification of the optimized structure model was confirmed using the ProSA web server (https://prosa.services.came.sbg.ac.at/prosa.php (accessed on 16 February 2022) and the ERRAT server (https://saves.mbi.ucla.edu/ (accessed on 16 February 2022) following our previous studies [8,23,26,27]. Potential protein structure errors were detected using the ProSA web server based on the Z-score, and a Z-score > 0 indicates that there may be an error or unstable part in the protein model.…”

“…Helper T lymphocyte (HTL) and cytotoxic T lymphocyte (CTL) epitopes were predicted from the selected LTBI-RD antigens using the MHC II server (http://tools.iedb. org/mhcii/ (accessed on 4 February 2022) and MHC I server (http://tools.iedb.org/mhci/ (accessed on 4 February 2022) in the IEDB database, respectively, following our previous studies [8,23,24,26,27]. HTL and CTL epitopes with percentile ranks < 0.5 were considered immunodominant.…”

“…Over the past century, BCG has remained the only licensed vaccine for the prevention of human TB, saving millions of lives and immunizing more people than any other vaccine [4,5]. However, the protective efficacy of BCG is highly variable, ranging from 0% to 80%, and the protection lasts only 10-20 years [4,[6][7][8][9]. Fortunately, new TB vaccines have been actively developed over past decades, such as inactivated, live attenuated, subunit, and viral vector-based TB vaccines [10,11].…”

Design and development of a multi‐epitope vaccine for the prevention of latent tuberculosis infection

“…As many B-cell epitopes are discontinuous, we used the ElliPro server (http://tools.iedb.org/ellipro/) to predict potential discontinuous B-cell epitopes of the candidate multi-epitope vaccine (MEV) based on our previous studies [13,33,36,37].…”