scholarly journals Epitope order Matters in multi-epitope-based peptide (MEBP) vaccine design: An in silico study

2021 ◽  
Author(s):  
Muthu Raj Salaikumaran ◽  
Prasanna Sudharson Kasamuthu ◽  
V L S Prasad Burra
Keyword(s):  
In Silico ◽  
Experimental Validation ◽  
Vaccine Development ◽  
Experimental Testing ◽  
Peptide Vaccine ◽  
Vaccine Design ◽  
Vaccine Candidates ◽  
Vaccine Potency ◽  
Experimental Protocols ◽  
The Many

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 candidate. 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, ranking, and 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. When the MEBP variants were ranked in descending order of their MVP scores, the published MEBPVC had the least MVP score. Further, the MEBP variants with IDs, SPVC_387 and SPVC_206, had the highest MVP scores indicating these variants to be more potent MEBPVCs than the published MEBPVC and hence should be prioritized for experimental testing and validation. Through this method, more vaccine candidates will be available for experimental validation and testing. This study also opens the opportunity to develop new software tools for designing more potent MEBPVCs in less time. The computationally validated top-ranked MEBPVCs must be experimentally tested, validated, and verified. The differences and deviations between experimental results and computational predictions provide an opportunity for improving and developing more efficient algorithms and reliable scoring schemes and software.

Novel Algorithms for In Silico Peptide Vaccine Design with Reference to Ebola Virus

2020 ◽  
Author(s):  
Subhamoy Biswas ◽  
Tathagata Dey ◽  
Shreyans Chatterjee ◽  
Smarajit Manna ◽  
Ashesh Nandy ◽  
...  
Keyword(s):  
In Silico ◽  
Ebola Virus ◽  
Peptide Vaccine ◽  
Vaccine Design ◽  
Novel Algorithms

scholarly journals Structural Basis for Designing Multiepitope Vaccines Against COVID-19 Infection: In Silico Vaccine Design and Validation (Preprint)

2020 ◽  
Author(s):  
Sukrit Srivastava ◽  
Sonia Verma ◽  
Mohit Kamthania ◽  
Rupinder Kaur ◽  
Ruchi Kiran Badyal ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Line ◽  
T Lymphocyte ◽  
Molecular Interactions ◽  
In Silico ◽  
Vaccine Design ◽  
Structural Basis ◽  
Toll Like Receptor ◽  
Vaccine Candidates ◽  
Line P

BACKGROUND The novel coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to the ongoing 2019-2020 pandemic. SARS-CoV-2 is a positive-sense single-stranded RNA coronavirus. Effective countermeasures against SARS-CoV-2 infection require the design and development of specific and effective vaccine candidates. OBJECTIVE To address the urgent need for a SARS-CoV-2 vaccine, in the present study, we designed and validated one cytotoxic T lymphocyte (CTL) and one helper T lymphocyte (HTL) multi-epitope vaccine (MEV) against SARS-CoV-2 using various in silico methods. METHODS Both designed MEVs are composed of CTL and HTL epitopes screened from 11 structural and nonstructural proteins of the SARS-CoV-2 proteome. Both MEVs also carry potential B-cell linear and discontinuous epitopes as well as interferon gamma–inducing epitopes. To enhance the immune response of our vaccine design, truncated (residues 10-153) <i>Onchocerca volvulus</i> activation-associated secreted protein-1 was used as an adjuvant at the N termini of both MEVs. The tertiary models for both the designed MEVs were generated, refined, and further analyzed for stable molecular interaction with toll-like receptor 3. Codon-biased complementary DNA (cDNA) was generated for both MEVs and analyzed in silico for high level expression in a mammalian (human) host cell line. RESULTS In the present study, we screened and shortlisted 38 CTL, 33 HTL, and 12 B cell epitopes from the 11 protein sequences of the SARS-CoV-2 proteome. Moreover, the molecular interactions of the screened epitopes with their respective human leukocyte antigen allele binders and the transporter associated with antigen processing (TAP) complex were positively validated. The shortlisted screened epitopes were utilized to design two novel MEVs against SARS-CoV-2. Further molecular models of both MEVs were prepared, and their stable molecular interactions with toll-like receptor 3 were positively validated. The codon-optimized cDNAs of both MEVs were also positively analyzed for high levels of overexpression in a human cell line. CONCLUSIONS The present study is highly significant in terms of the molecular design of prospective CTL and HTL vaccines against SARS-CoV-2 infection with potential to elicit cellular and humoral immune responses. The epitopes of the designed MEVs are predicted to cover the large human population worldwide (96.10%). Hence, both designed MEVs could be tried in vivo as potential vaccine candidates against SARS-CoV-2.

scholarly journals In silico discovery of antigenic proteins and epitopes of SARS-CoV-2 for the development of a vaccine or a diagnostic approach for COVID-19

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hüseyin Can ◽  
Ahmet Efe Köseoğlu ◽  
Sedef Erkunt Alak ◽  
Mervenur Güvendi ◽  
Mert Döşkaya ◽  
...  
Keyword(s):  
Signal Peptide ◽  
In Silico ◽  
Transmembrane Helix ◽  
Peptide Vaccine ◽  
Surface Proteins ◽  
Structural Proteins ◽  
Mhc I ◽  
Vaccine Candidates ◽  
Antigenic Proteins ◽  
Aliphatic Index

AbstractIn the genome of SARS-CoV-2, the 5′-terminus encodes a polyprotein, which is further cleaved into 15 non-structural proteins whereas the 3′ terminus encodes four structural proteins and eight accessory proteins. Among these 27 proteins, the present study aimed to discover likely antigenic proteins and epitopes to be used for the development of a vaccine or serodiagnostic assay using an in silico approach. For this purpose, after the full genome analysis of SARS-CoV-2 Wuhan isolate and variant proteins that are detected frequently, surface proteins including spike, envelope, and membrane proteins as well as proteins with signal peptide were determined as probable vaccine candidates whereas the remaining were considered as possible antigens to be used during the development of serodiagnostic assays. According to results obtained, among 27 proteins, 26 of them were predicted as probable antigen. In 26 proteins, spike protein was selected as the best vaccine candidate because of having a signal peptide, negative GRAVY value, one transmembrane helix, moderate aliphatic index, a big molecular weight, a long-estimated half-life, beta wrap motifs as well as having stable, soluble and non-allergic features. In addition, orf7a, orf8, and nsp-10 proteins with signal peptide were considered as potential vaccine candidates. Nucleocapsid protein and a highly antigenic GGDGKMKD epitope were identified as ideal antigens to be used in the development of serodiagnostic assays. Moreover, considering MHC-I alleles, highly antigenic KLNDLCFTNV and ITLCFTLKRK epitopes can be used to develop an epitope-based peptide vaccine.

Identification of Generalized Peptide Regions for Designing Vaccine Effective for All Significant Mutated Strains of SARS-CoV-2

2021 ◽  
Vol 24 ◽  
Author(s):  
Subhamoy Biswas ◽  
Smarajit Manna ◽  
Tathagata Dey ◽  
Shreyans Chatterjee ◽  
Sumanta Dey
Keyword(s):  
Comparative Study ◽  
Zika Virus ◽  
Peptide Vaccine ◽  
Vaccine Design ◽  
Current Approach ◽  
Polar Plot ◽  
Vaccine Candidates ◽  
The Future ◽  
Potential Vaccine ◽  
The Comparative Study

Background: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has become a worldwide pandemic and created an utmost crisis across the globe. To mitigate the crisis, the design of vaccines is a crucial solution. The frequent mutation of the virus demands generalized vaccine candidates, which would be effective for all mutated strains at present and for the strains that would evolve due to further new mutations in the virus. Objective: The objective of this study is to identify more frequently occurring mutated variants of SARS-CoV-2 and to suggest peptide vaccine candidates effective in common against the viral strains considered. Method: In this study, we have identified all currently prevailing mutated strains of SARS-CoV-2 through 2D Polar plot and Quotient Radius〖(q〗_R) characterization descriptor. Then, by considering the top eight mutation strains, which are significant due to their frequency of occurrence, peptide regions suitable for vaccine design have been identified with the help of a mathematical model – 2D Polygon Representation, followed by the evaluation of epitope potential and ensuring that there is no case of any autoimmune threat. Lastly, in order to verify whether this entire approach is applicable for vaccine design against any other virus in general, we have made a comparative study between the peptide vaccine candidates prescribed for the Zika virus using the current approach and a list of potential vaccine candidates for the same already established in the past. Results: We have finally suggested three generalized peptide regions which would be suitable as sustainable peptide vaccine candidates against SARS-CoV-2 irrespective of its currently prevailing strains as well any other variant of the same that may appear in the future. We also observed that during the comparative study using the case of E protein of Zika virus, the peptide regions suggested using the new approach matched with the already established results. Conclusion: The study, therefore, illustrates an approach that would help in developing peptide vaccine against SARS-CoV-2 by suggesting those peptide regions which can be targeted irrespective of any mutated form of this virus. The consistency with which this entire approach was also able to figure out similar vaccine candidates for Zika virus with utmost accuracy proves that this protocol can be extended for peptide vaccine design against any other virus in the future.

scholarly journals Immunoinformatics Approach for Epitope-Based Peptide Vaccine Design and Active Site Prediction against Polyprotein of Emerging Oropouche Virus

2018 ◽  
Vol 2018 ◽  
pp. 1-22 ◽  
Author(s):  
Utpal Kumar Adhikari ◽  
Mourad Tayebi ◽  
M. Mizanur Rahman
Keyword(s):  
T Cell ◽  
Ligand Binding ◽  
B Cell ◽  
Peptide Vaccine ◽  
Vaccine Design ◽  
Binding Interaction ◽  
B Cell Epitopes ◽  
Vaccine Candidates ◽  
Binding Pockets ◽  
Potential Vaccine

Oropouche virus (OROV) is an emerging pathogen which causes Oropouche fever and meningitis in humans. Several outbreaks of OROV in South America, especially in Brazil, have changed its status as an emerging disease, but no vaccine or specific drug target is available yet. Our approach was to identify the epitope-based vaccine candidates as well as the ligand-binding pockets through the use of immunoinformatics. In this report, we identified both T-cell and B-cell epitopes of the most antigenic OROV polyprotein with the potential to induce both humoral and cell-mediated immunity. Eighteen highly antigenic and immunogenic CD8+ T-cell epitopes were identified, including three 100% conserved epitopes (TSSWGCEEY, CSMCGLIHY, and LAIDTGCLY) as the potential vaccine candidates. The selected epitopes showed 95.77% coverage for the mixed Brazilian population. The docking simulation ensured the binding interaction with high affinity. A total of five highly conserved and nontoxic linear B-cell epitopes “NQKIDLSQL,” “HPLSTSQIGDRC,” “SHCNLEFTAITADKIMSL,” “PEKIPAKEGWLTFSKEHTSSW,” and “HHYKPTKNLPHVVPRYH” were selected as potential vaccine candidates. The predicted eight conformational B-cell epitopes represent the accessibility for the entered virus. In the posttherapeutic strategy, ten ligand-binding pockets were identified for effective inhibitor design against emerging OROV infection. Collectively, this research provides novel candidates for epitope-based peptide vaccine design against OROV.

scholarly journals An in silico epitope-based peptide vaccine design against the 2019-nCoV

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Olanrewaju Ayodeji Durojaye ◽  
Talifhani Mushiana ◽  
Samuel Cosmas ◽  
Glory Omini Ibiang ◽  
Mercy Omini Ibiang
Keyword(s):  
In Silico ◽  
Peptide Vaccine ◽  
Vaccine Design

scholarly journals In Silico Approach for Peptide Vaccine Design for CoVID 19

2020 ◽  
Author(s):  
Subhamoy Biswas ◽  
Shreyans Chatterjee ◽  
Tathagata Dey ◽  
Sumanta Dey ◽  
Smarajit Manna ◽  
...  
Keyword(s):  
In Silico ◽  
Peptide Vaccine ◽  
Vaccine Design
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