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Exploring the out of sight antigens of SARS-CoV-2 to design a candidate multi-epitope vaccine by utilizing immunoinformatics approaches.
Vaccine. 2020 11 10; 38(48):7612-7628.V

Abstract

SARS-CoV-2 causes a severe respiratory disease called COVID-19. Currently, global health is facing its devastating outbreak. However, there is no vaccine available against this virus up to now. In this study, a novel multi-epitope vaccine against SARS-CoV-2 was designed to provoke both innate and adaptive immune responses. The immunodominant regions of six non-structural proteins (nsp7, nsp8, nsp9, nsp10, nsp12 and nsp14) of SARS-CoV-2 were selected by multiple immunoinformatic tools to provoke T cell immune response. Also, immunodominant fragment of the functional region of SARS-CoV-2 spike (400-510 residues) protein was selected for inducing neutralizing antibodies production. The selected regions' sequences were connected to each other by furin-sensitive linker (RVRR). Moreover, the functional region of β-defensin as a well-known agonist for the TLR-4/MD complex was added at the N-terminus of the vaccine using (EAAAK)3 linker. Also, a CD4 + T-helper epitope, PADRE, was used at the C-terminal of the vaccine by GPGPG and A(EAAAK)2A linkers to form the final vaccine construct. The physicochemical properties, allergenicity, antigenicity, functionality and population coverage of the final vaccine construct were analyzed. The final vaccine construct was an immunogenic, non-allergen and unfunctional protein which contained multiple CD8 + and CD4 + overlapping epitopes, IFN-γ inducing epitopes, linear and conformational B cell epitopes. It could form stable and significant interactions with TLR-4/MD according to molecular docking and dynamics simulations. Global population coverage of the vaccine for HLA-I and II were estimated 96.2% and 97.1%, respectively. At last, the final vaccine construct was reverse translated to design the DNA vaccine. Although the designed vaccine exhibited high efficacy in silico, further experimental validation is necessary.

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Authors+Show Affiliations

Safavi A
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Kefayat A
Department of Oncology, Cancer Prevention Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Mahdevar E
Department of Biology, Faculty of Science and Engineering, Science and Arts University, Yazd, Iran.
Abiri A
Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
Ghahremani F
Department of Medical Physics and Radiotherapy, Arak School of Paramedicine, Arak University of Medical Sciences, Arak, Iran. Electronic address: F.ghahremani@arakmu.ac.ir.

MeSH

Amino Acid SequenceAntibodies, ViralBetacoronavirusCOVID-19COVID-19 VaccinesComputational BiologyCoronavirus InfectionsEpitopes, B-LymphocyteEpitopes, T-LymphocyteHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHumansImmunity, InnateImmunogenicity, VaccineMolecular Docking SimulationPandemicsPneumonia, ViralProtein BindingProtein Structure, SecondarySARS-CoV-2Spike Glycoprotein, CoronavirusVaccines, AttenuatedVaccines, DNAVaccines, SubunitViral Nonstructural ProteinsViral Vaccines

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33082015

Citation

Safavi, Ashkan, et al. "Exploring the Out of Sight Antigens of SARS-CoV-2 to Design a Candidate Multi-epitope Vaccine By Utilizing Immunoinformatics Approaches." Vaccine, vol. 38, no. 48, 2020, pp. 7612-7628.
Safavi A, Kefayat A, Mahdevar E, et al. Exploring the out of sight antigens of SARS-CoV-2 to design a candidate multi-epitope vaccine by utilizing immunoinformatics approaches. Vaccine. 2020;38(48):7612-7628.
Safavi, A., Kefayat, A., Mahdevar, E., Abiri, A., & Ghahremani, F. (2020). Exploring the out of sight antigens of SARS-CoV-2 to design a candidate multi-epitope vaccine by utilizing immunoinformatics approaches. Vaccine, 38(48), 7612-7628. https://doi.org/10.1016/j.vaccine.2020.10.016
Safavi A, et al. Exploring the Out of Sight Antigens of SARS-CoV-2 to Design a Candidate Multi-epitope Vaccine By Utilizing Immunoinformatics Approaches. Vaccine. 2020 11 10;38(48):7612-7628. PubMed PMID: 33082015.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exploring the out of sight antigens of SARS-CoV-2 to design a candidate multi-epitope vaccine by utilizing immunoinformatics approaches. AU - Safavi,Ashkan, AU - Kefayat,Amirhosein, AU - Mahdevar,Elham, AU - Abiri,Ardavan, AU - Ghahremani,Fatemeh, Y1 - 2020/10/09/ PY - 2020/05/05/received PY - 2020/08/25/revised PY - 2020/10/06/accepted PY - 2020/10/22/pubmed PY - 2020/11/13/medline PY - 2020/10/21/entrez KW - COVID-19 KW - Immunoinformatics KW - In silico KW - SARS-CoV-2 KW - Vaccine SP - 7612 EP - 7628 JF - Vaccine JO - Vaccine VL - 38 IS - 48 N2 - SARS-CoV-2 causes a severe respiratory disease called COVID-19. Currently, global health is facing its devastating outbreak. However, there is no vaccine available against this virus up to now. In this study, a novel multi-epitope vaccine against SARS-CoV-2 was designed to provoke both innate and adaptive immune responses. The immunodominant regions of six non-structural proteins (nsp7, nsp8, nsp9, nsp10, nsp12 and nsp14) of SARS-CoV-2 were selected by multiple immunoinformatic tools to provoke T cell immune response. Also, immunodominant fragment of the functional region of SARS-CoV-2 spike (400-510 residues) protein was selected for inducing neutralizing antibodies production. The selected regions' sequences were connected to each other by furin-sensitive linker (RVRR). Moreover, the functional region of β-defensin as a well-known agonist for the TLR-4/MD complex was added at the N-terminus of the vaccine using (EAAAK)3 linker. Also, a CD4 + T-helper epitope, PADRE, was used at the C-terminal of the vaccine by GPGPG and A(EAAAK)2A linkers to form the final vaccine construct. The physicochemical properties, allergenicity, antigenicity, functionality and population coverage of the final vaccine construct were analyzed. The final vaccine construct was an immunogenic, non-allergen and unfunctional protein which contained multiple CD8 + and CD4 + overlapping epitopes, IFN-γ inducing epitopes, linear and conformational B cell epitopes. It could form stable and significant interactions with TLR-4/MD according to molecular docking and dynamics simulations. Global population coverage of the vaccine for HLA-I and II were estimated 96.2% and 97.1%, respectively. At last, the final vaccine construct was reverse translated to design the DNA vaccine. Although the designed vaccine exhibited high efficacy in silico, further experimental validation is necessary. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/33082015/Exploring_the_out_of_sight_antigens_of_SARS_CoV_2_to_design_a_candidate_multi_epitope_vaccine_by_utilizing_immunoinformatics_approaches_ DB - PRIME DP - Unbound Medicine ER -