An in silico approach to study the role of epitope order in the multi-epitope-based peptide (MEBP) vaccine design

Abstract

With different countries facing multiple waves, with some SARS-CoV-2 variants more deadly and virulent, the COVID-19 pandemic is becoming more dangerous by the day and the world is facing an even more dreadful extended pandemic with exponential positive cases and increasing death rates. There is an urgent need for more efficient and faster methods of vaccine development against SARS-CoV-2. Compared to experimental protocols, the opportunities to innovate are very high in immunoinformatics/in silico approaches, especially with the recent adoption of structural bioinformatics in peptide vaccine design. In recent times, multi-epitope-based peptide vaccine candidates (MEBPVCs) have shown extraordinarily high humoral and cellular responses to immunization. Most of the publications claim that respective reported MEBPVC(s) assembled using a set of in silico predicted epitopes, to be the computationally validated potent vaccine candidate(s) ready for experimental validation. However, in this article, for a given set of predicted epitopes, it is shown that the published MEBPVC is one among the many possible variants and there is high likelihood of finding more potent MEBPVCs than the published candidates. To test the same, a methodology is developed where novel MEBP variants are derived by changing the epitope order of the published MEBPVC. Further, to overcome the limitations of current qualitative methods of assessment of MEBPVC, to enable quantitative comparison and ranking for the discovery of more potent MEBPVCs, novel predictors, Percent Epitope Accessibility (PEA), Receptor specific MEBP vaccine potency (RMVP), MEBP vaccine potency (MVP) are introduced. The MEBP variants indeed showed varied MVP scores indicating varied immunogenicity. Further, the MEBP variants with IDs, SPVC_446 and SPVC_537, had the highest MVP scores indicating these variants to be more potent MEBPVCs than the published MEBPVC and hence should be preferred candidates for immediate experimental testing and validation. The method enables quicker selection and high throughput experimental validation of vaccine candidates. This study also opens the opportunity to develop new software tools for designing more potent MEBPVCs in less time.

Integration: Gospel for immune bioinformatician on epitope-based therapy

“…It would not be state-of-art to present the whole things directly in the main text. By looking at these data using a holistic view, that is, using a heatmap form, which can show three dimensions: the epitopes, MHC genotypes and affinity ranks ( 40 , 41 ). It is intuitive to exhibit the epitopes that are dominant in MHC genotypes.…”

The Construction of A Multi-epitope Vaccine Against Klebsiella pneumoniae Using in silico Approach

“…The prediction of solvent accessibility shows results above 55% which indicates that the high possibility of a vaccine being immunogenic. 26 The results of modeling using the I-TASSER webserver are then refined to improve the most favored regions, which shows the stability of the structure. Furthermore, the perfected vaccine molecule is docked with the TLR2 molecule.…”

Multi Epitopic Peptide Based Vaccine Development Targeting Immobilization Antigen of Ichthyophthirius multifiliis: A Computational Approach

“…MEBP vaccines are proved to be effective against cancer, filarial disease, multi-drug resistance pathogens, Tuberculosis, COVID-19, malaria and many more. These vaccines furnishes better options to provide immunogenicity, reproducibility and experimental control over antigenic protein of pathogens (Salaikumaran, et al 2022 ). In the modern science, proteomic data of different pathogen which is easily and widely available in globally used software and server came into play.…”