Structural basis of development of multi-epitope vaccine against Middle East respiratory syndrome using in silico approach
Identifieur interne : 000692 ( Main/Exploration ); précédent : 000691; suivant : 000693Structural basis of development of multi-epitope vaccine against Middle East respiratory syndrome using in silico approach
Auteurs : Sukrit Srivastava ; Mohit Kamthania [Inde] ; Soni Singh ; Ajay K. Saxena ; Nishi SharmaSource :
- Infection and Drug Resistance [ 1178-6973 ] ; 2018.
Abstract
Middle East respiratory syndrome (MERS) is caused by MERS coronavirus (MERS-CoV). Thus far, MERS outbreaks have been reported from Saudi Arabia (2013 and 2014) and South Korea (2015). No specific vaccine has yet been reported against MERS.
To address the urgent need for an MERS vaccine, in the present study, we have designed two multi-epitope vaccines (MEVs) against MERS utilizing several in silico methods and tools.
The design of both the multi-epitope vaccines (MEVs) are composed of cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes, screened form thirteen different proteins of MERS-CoV. Both the MEVs also carry potential B-cell linear epitope regions, B-cell discontinuous epitopes as well as interferon-γ-inducing epitopes. Human β-defensin-2 and β-defensin-3 were used as adjuvants to enhance the immune response of MEVs. To design the MEVs, short peptide molecular linkers were utilized to link screened most potential CTL epitopes, HTL epitopes and the adjuvants. Tertiary models for both the MEVs were generated, refined, and further studied for their molecular interaction with toll-like receptor 3. The cDNAs of both MEVs were generated and analyzed in silico for their expression in a mammalian host cell line (human).
Screened CTL and HTL epitopes were found to have high propensity for stable molecular interaction with HLA alleles molecules. CTL epitopes were also found to have favorable molecular interaction within the cavity of transporter associated with antigen processing. The selected CTL and HTL epitopes jointly cover upto 94.0% of worldwide human population. Both the CTL and HTL MEVs molecular models have shown to have stable binding and complex formation propensity with toll-like receptor 3. The cDNA analysis of both the MEVs have shown high expression tendency in mammalian host cell line (human).
After multistage in silico analysis, both the MEVs are predicted to elicit humoral as well as cell mediated immune response. Epitopes of the designed MEVs are predicted to cover large human population worldwide. Hence both the designed MEVs could be tried in vivo as potential vaccine candidates against MERS.
Url:
DOI: 10.2147/IDR.S175114
PubMed: 30538505
PubMed Central: 6254671
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Structural basis of development of multi-epitope vaccine against Middle East respiratory syndrome using in silico approach</title><author><name sortKey="Srivastava, Sukrit" sort="Srivastava, Sukrit" uniqKey="Srivastava S" first="Sukrit" last="Srivastava">Sukrit Srivastava</name><affiliation><nlm:aff id="af1-idr-11-2377">Department of Biotechnology, Mangalayatan University, Aligarh, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation><affiliation><nlm:aff id="af2-idr-11-2377">Molecular Medicine Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Kamthania, Mohit" sort="Kamthania, Mohit" uniqKey="Kamthania M" first="Mohit" last="Kamthania">Mohit Kamthania</name><affiliation><nlm:aff id="af1-idr-11-2377">Department of Biotechnology, Mangalayatan University, Aligarh, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-idr-11-2377">Department of Biotechnology, Faculty of Life Sciences, Institute of Applied Medicines and Research, Ghaziabad, Uttar Pradesh, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Biotechnology, Faculty of Life Sciences, Institute of Applied Medicines and Research, Ghaziabad, Uttar Pradesh</wicri:regionArea><wicri:noRegion>Uttar Pradesh</wicri:noRegion></affiliation></author><author><name sortKey="Singh, Soni" sort="Singh, Soni" uniqKey="Singh S" first="Soni" last="Singh">Soni Singh</name><affiliation><nlm:aff id="af1-idr-11-2377">Department of Biotechnology, Mangalayatan University, Aligarh, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Saxena, Ajay K" sort="Saxena, Ajay K" uniqKey="Saxena A" first="Ajay K" last="Saxena">Ajay K. Saxena</name><affiliation><nlm:aff id="af2-idr-11-2377">Molecular Medicine Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Sharma, Nishi" sort="Sharma, Nishi" uniqKey="Sharma N" first="Nishi" last="Sharma">Nishi Sharma</name><affiliation><nlm:aff id="af1-idr-11-2377">Department of Biotechnology, Mangalayatan University, Aligarh, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30538505</idno><idno type="pmc">6254671</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254671</idno><idno type="RBID">PMC:6254671</idno><idno type="doi">10.2147/IDR.S175114</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000596</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000596</idno><idno type="wicri:Area/Pmc/Curation">000596</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000596</idno><idno type="wicri:Area/Pmc/Checkpoint">000111</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000111</idno><idno type="wicri:Area/Ncbi/Merge">000742</idno><idno type="wicri:Area/Ncbi/Curation">000742</idno><idno type="wicri:Area/Ncbi/Checkpoint">000742</idno><idno type="wicri:Area/Main/Merge">000694</idno><idno type="wicri:Area/Main/Curation">000692</idno><idno type="wicri:Area/Main/Exploration">000692</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Structural basis of development of multi-epitope vaccine against Middle East respiratory syndrome using in silico approach</title><author><name sortKey="Srivastava, Sukrit" sort="Srivastava, Sukrit" uniqKey="Srivastava S" first="Sukrit" last="Srivastava">Sukrit Srivastava</name><affiliation><nlm:aff id="af1-idr-11-2377">Department of Biotechnology, Mangalayatan University, Aligarh, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation><affiliation><nlm:aff id="af2-idr-11-2377">Molecular Medicine Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Kamthania, Mohit" sort="Kamthania, Mohit" uniqKey="Kamthania M" first="Mohit" last="Kamthania">Mohit Kamthania</name><affiliation><nlm:aff id="af1-idr-11-2377">Department of Biotechnology, Mangalayatan University, Aligarh, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-idr-11-2377">Department of Biotechnology, Faculty of Life Sciences, Institute of Applied Medicines and Research, Ghaziabad, Uttar Pradesh, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Biotechnology, Faculty of Life Sciences, Institute of Applied Medicines and Research, Ghaziabad, Uttar Pradesh</wicri:regionArea><wicri:noRegion>Uttar Pradesh</wicri:noRegion></affiliation></author><author><name sortKey="Singh, Soni" sort="Singh, Soni" uniqKey="Singh S" first="Soni" last="Singh">Soni Singh</name><affiliation><nlm:aff id="af1-idr-11-2377">Department of Biotechnology, Mangalayatan University, Aligarh, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Saxena, Ajay K" sort="Saxena, Ajay K" uniqKey="Saxena A" first="Ajay K" last="Saxena">Ajay K. Saxena</name><affiliation><nlm:aff id="af2-idr-11-2377">Molecular Medicine Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation></author><author><name sortKey="Sharma, Nishi" sort="Sharma, Nishi" uniqKey="Sharma N" first="Nishi" last="Sharma">Nishi Sharma</name><affiliation><nlm:aff id="af1-idr-11-2377">Department of Biotechnology, Mangalayatan University, Aligarh, India,<email>srivastav.sukrit@gmail.com</email></nlm:aff></affiliation></author></analytic><series><title level="j">Infection and Drug Resistance</title><idno type="eISSN">1178-6973</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Middle East respiratory syndrome (MERS) is caused by MERS coronavirus (MERS-CoV). Thus far, MERS outbreaks have been reported from Saudi Arabia (2013 and 2014) and South Korea (2015). No specific vaccine has yet been reported against MERS.</p></sec><sec><title>Purpose</title><p>To address the urgent need for an MERS vaccine, in the present study, we have designed two multi-epitope vaccines (MEVs) against MERS utilizing several in silico methods and tools.</p></sec><sec><title>Methods</title><p>The design of both the multi-epitope vaccines (MEVs) are composed of cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes, screened form thirteen different proteins of MERS-CoV. Both the MEVs also carry potential B-cell linear epitope regions, B-cell discontinuous epitopes as well as interferon-γ-inducing epitopes. Human β-defensin-2 and β-defensin-3 were used as adjuvants to enhance the immune response of MEVs. To design the MEVs, short peptide molecular linkers were utilized to link screened most potential CTL epitopes, HTL epitopes and the adjuvants. Tertiary models for both the MEVs were generated, refined, and further studied for their molecular interaction with toll-like receptor 3. The cDNAs of both MEVs were generated and analyzed in silico for their expression in a mammalian host cell line (human).</p></sec><sec><title>Results</title><p>Screened CTL and HTL epitopes were found to have high propensity for stable molecular interaction with HLA alleles molecules. CTL epitopes were also found to have favorable molecular interaction within the cavity of transporter associated with antigen processing. The selected CTL and HTL epitopes jointly cover upto 94.0% of worldwide human population. Both the CTL and HTL MEVs molecular models have shown to have stable binding and complex formation propensity with toll-like receptor 3. The cDNA analysis of both the MEVs have shown high expression tendency in mammalian host cell line (human).</p></sec><sec><title>Conclusion</title><p>After multistage in silico analysis, both the MEVs are predicted to elicit humoral as well as cell mediated immune response. Epitopes of the designed MEVs are predicted to cover large human population worldwide. 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uniqKey="Alshukairi A">AN Alshukairi</name></author><author><name sortKey="Baharoon, Sa" uniqKey="Baharoon S">SA Baharoon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Robinson, J" uniqKey="Robinson J">J Robinson</name></author><author><name sortKey="Halliwell, Ja" uniqKey="Halliwell J">JA Halliwell</name></author><author><name sortKey="Hayhurst, Jd" uniqKey="Hayhurst J">JD Hayhurst</name></author><author><name sortKey="Flicek, P" uniqKey="Flicek P">P Flicek</name></author><author><name sortKey="Parham, P" uniqKey="Parham P">P Parham</name></author><author><name sortKey="Marsh, Sg" uniqKey="Marsh S">SG Marsh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, D" uniqKey="Xu D">D Xu</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Inde</li></country></list><tree><noCountry><name sortKey="Saxena, Ajay K" sort="Saxena, Ajay K" uniqKey="Saxena A" first="Ajay K" last="Saxena">Ajay K. Saxena</name><name sortKey="Sharma, Nishi" sort="Sharma, Nishi" uniqKey="Sharma N" first="Nishi" last="Sharma">Nishi Sharma</name><name sortKey="Singh, Soni" sort="Singh, Soni" uniqKey="Singh S" first="Soni" last="Singh">Soni Singh</name><name sortKey="Srivastava, Sukrit" sort="Srivastava, Sukrit" uniqKey="Srivastava S" first="Sukrit" last="Srivastava">Sukrit Srivastava</name></noCountry><country name="Inde"><noRegion><name sortKey="Kamthania, Mohit" sort="Kamthania, Mohit" uniqKey="Kamthania M" first="Mohit" last="Kamthania">Mohit Kamthania</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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