Abstract
This paper presents an alternative vaccination platform that provides long-term cellular immune protection mediated by cytotoxic T-cells. The immune response via cellular immunity creates superior resistance to viral mutations, which are currently the greatest threat to the global vaccination campaign. Furthermore, we also propose a safer, more facile, and physiologically appropriate immunization method using either intranasal or oral administration. The underlying technology is an adaptation of synthetic long peptides (SLPs) previously used in cancer immunotherapy. The overall quality of the SLP constructs was validated using in silico methods. SLPs comprising HLA class I and class II epitopes were designed to stimulate antigen cross-presentation and canonical class II presentation by dendritic cells. The desired effect is a cytotoxic T cell-mediated prompt and specific immune response against the virus-infected epithelia and a rapid and robust virus clearance. Epitopes isolated from COVID-19 convalescent patients were screened for HLA class I and class II binding (NetMHCpan and NetMHCIIpan) and highest HLA population coverage (IEDB Population Coverage). 15 class I and 4 class II epitopes were identified and used for this SLP design. The constructs were characterized based on their toxicity (ToxinPred), allergenicity (AllerCatPro), immunogenicity (VaxiJen 2.0), and physico-chemical parameters (ProtParam). Based on in silico predictions, out of 60 possible SLPs, 36 candidate structures presented a high probability to be immunogenic, non-allergenic, non-toxic, and stable. 3D peptide folding followed by 3D structure validation (PROCHECK) and molecular docking studies (HADDOCK 2.4) with Toll-like receptors 2 and 4 provided positive results, suggestive for favorable antigen presentation and immune stimulation.
Highlights
Introduction iationsSARS-CoV-2 is an RNA virus responsible for the current COVID-19 pandemic
Nineteen peptides were identified based on the degree of conservation >0.85, low percentile rank on NetMHCpan and NetMHCIIpan, and cross-specificity: 15 HLA class
Most epitopes originated from the S protein (13/19, 68.42%) and M protein (4/19, 21.05%), probably due to their position on the viral surface membrane facilitating antigen recognition. (Table 1) Interestingly, peptides originating from the inner core, such as ORF1a or N were identified in COVID-19-convalescent patients
Summary
I were extracted extractedfrom fromaapeptide peptidepool poolcomprising comprising. The peptide peptide pool database here: https://www.mckayspcb.com/SARS2 can be accessed here: TcellEpitopes/. Peptide(accessed screeningonwas based on the following https://www.mckayspcb.com/SARS2TcellEpitopes/
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