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Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch vaccines, designed by reverse epitomics approach, show potential to cover large ethnically distributed human population worldwide.
Srivastava, Sukrit Verma, Sonia Kamthania, Mohit Agarwal, Deepa Saxena, Ajay Kumar Kolbe, Michael Singh, Sarman Kotnis, Ashwin Rathi, Brijesh Nayar, Seema A
Srivastava, Sukrit
Verma, Sonia
Kamthania, Mohit
Agarwal, Deepa
Saxena, Ajay Kumar
Kolbe, Michael
Singh, Sarman
Kotnis, Ashwin
Rathi, Brijesh
Nayar, Seema A
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2020-11-06
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Abstract
The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is responsible for the COVID-19 outbreak. The highly contagious COVID-19 disease has spread to 216 countries in less than six months. Though several vaccine candidates are being claimed, an effective vaccine is yet to come. A novel reverse epitomics approach, 'overlapping-epitope-clusters-to-patches' method is utilized to identify the antigenic regions from the SARS-CoV-2 proteome. These antigenic regions are named as 'Ag-Patch or Ag-Patches', for Antigenic Patch or Patches. The identification of Ag-Patches is based on the clusters of overlapping epitopes rising from SARS-CoV-2 proteins. Further, we have utilized the identified Ag-Patches to design Multi-Patch Vaccines (MPVs), proposing a novel method for the vaccine design. The designed MPVs were analyzed for immunologically crucial parameters, physiochemical properties and cDNA constructs. We identified 73 CTL (Cytotoxic T-Lymphocyte) and 49 HTL (Helper T-Lymphocyte) novel Ag-Patches from the proteome of SARS-CoV-2. The identified Ag-Patches utilized to design MPVs cover 768 overlapping epitopes targeting 55 different HLA alleles leading to 99.98% of world human population coverage. The MPVs and Toll-Like Receptor ectodomain complex shows stable complex formation tendency. Further, the cDNA analysis favors high expression of the MPVs constructs in a human cell line. We identified highly immunogenic novel Ag-Patches from the entire proteome of SARS CoV-2 by a novel reverse epitomics approach and utilized them to design MPVs. We conclude that the novel MPVs could be a highly potential novel approach to combat SARS-CoV-2, with greater effectiveness, high specificity and large human population coverage worldwide.
Citation
J Biomol Struct Dyn. 2020 Nov 6:1-20. doi: 10.1080/07391102.2020.1838329. Epub ahead of print.
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en
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1538-0254
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Attribution-NonCommercial-ShareAlike 4.0 International