In silico rational design of a novel tetra-epitope tetanus vaccine with complete population coverage using developed immunoinformatics and surface epitope mapping approaches

• Published in: Medical hypotheses 2019-09, Vol.130, p.109267-109267, Article 109267
• Main Authors: Bazmara, Samira, Shadmani, Mahsa, Ghasemnejad, Atefeh, Aghazadeh, Hossein, Pooshang Bagheri, Kamran
• Format: Article
• Language: English
• Subjects: Alleles; Allergy and Immunology - instrumentation; Computational Biology; Docking; Drug Design; Epitope Mapping - methods; Epitopes; HLA Antigens - immunology; HLA-DP Antigens - immunology; HLA-DQ Antigens - immunology; HLA-DRB1 Chains - immunology; Humans; Immunoinformatics; Molecular Conformation; Molecular Docking Simulation; Multi-epitope; Population coverage; Surface epitopes; Tetanus; Tetanus Toxoid - chemistry; Vaccine designing
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1016/j.mehy.2019.109267

Presentation of many unwanted epitopes within tetanus toxoid vaccine to lymphocyte clones may lead to production of many unwanted antibodies. Moreover an ideal vaccine must cover all individuals in a population that is dependent to the kinds of human leukocyte antigen alleles. Concerning these issues, our study was aimed to in silico design of a multi-epitope tetanus vaccine (METV) in order to improve population coverage and protectivity of tetanus vaccine as well as reduction of complications. Concerning these issues, a novel rational filtration was implemented to design a novel METV using immunoinformatics and surface epitope mapping approaches. Prediction of epitopes for tetanus toxin was performed in the candidate country in which the frequency had been gathered from almost all geographical distributions. The most strong binder epitopes for major histocompatibility complex class II were selected and among them the surface epitopes of native toxin were selected. The population coverage of the selected epitopes was estimated. The final candidate epitopes had highly population coverage. Molecular docking was performed to prediction of binding affinity of our candidate epitopes to the HLA-DRB1 alleles. At first, 680 strong binder epitopes were predicted. Among them 11 epitopes were selected. Finally, 4 epitopes had the most population coverage and suggested as a tetra-epitope tetanus vaccine. 99.41% of inessential strong binders were deleted using our tree steps filtration. HLA-DP had the most roles in epitope presentation. Molecular docking analysis proved the strong binding affinity of candidate epitopes to the HLA-DRB1 alleles. In conclusion, we theoretically reduced 99.41% of unwanted antibodies using our novel filtration strategies. Our tetra-epitope tetanus vaccine showed 100% population coverage in the candidate country. Furthermore, it was demonstrated that HLA-DP and HLA-DQ had more potential in epitope presentation in comparison to HLA-DRB1.