Immunoinformatics Analysis of SARS-CoV-2 ORF1ab Polyproteins to Identify Promiscuous and Highly Conserved T-Cell...

SARS-CoV-2 and its variants caused the COVID-19 pandemic. Vaccines that target conserved regions of SARS-CoV-2 and stimulate protective T-cell responses are important for reducing symptoms and limiting the infection. Seven cytotoxic (CTL) and five helper T-cells (HTL) epitopes from ORF1ab were identified using NetCTLpan and NetMHCIIpan algorithms, respectively. These epitopes were generated from ORF1ab regions that are evolutionary stable as reflected by zero Shannon's entropy and are presented by 56 human leukocyte antigen (HLA) Class I and 22 HLA Class II, ensuring good coverage for the Indonesian and world population. Having fulfilled other criteria such as immunogenicity, IFNγ inducing ability, and non-homology to human and microbiome peptides, the epitopes were assembled into a vaccine construct (VC) together with β-defensin as adjuvant and appropriate linkers. The VC was shown to have good physicochemical characteristics and capability of inducing CTL as well as HTL responses, which stem from the engagement of the vaccine with toll-like receptor 4 (TLR4) as revealed by docking simulations. The most promiscuous peptide ⁸⁹⁹WSMATYYLF⁹⁰⁷ was shown via docking simulation to interact well with HLA-A*24:07, the most predominant allele in Indonesia. The data presented here will contribute to the in vitro study of T-cell epitope mapping and vaccine design in Indonesia.