PMID- 34960205 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231108 IS - 2076-393X (Print) IS - 2076-393X (Electronic) IS - 2076-393X (Linking) VI - 9 IP - 12 DP - 2021 Dec 9 TI - Immunoinformatics Analysis of SARS-CoV-2 ORF1ab Polyproteins to Identify Promiscuous and Highly Conserved T-Cell Epitopes to Formulate Vaccine for Indonesia and the World Population. LID - 10.3390/vaccines9121459 [doi] LID - 1459 AB - 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, IFNgamma inducing ability, and non-homology to human and microbiome peptides, the epitopes were assembled into a vaccine construct (VC) together with beta-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 (899)WSMATYYLF(907) 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. FAU - Gustiananda, Marsia AU - Gustiananda M AD - Department of Biomedicine, School of Life Sciences, Indonesia International Institute for Life Sciences, Jl. Pulomas Barat Kav 88, Jakarta 13210, Indonesia. FAU - Sulistyo, Bobby Prabowo AU - Sulistyo BP AUID- ORCID: 0000-0002-5203-4822 AD - Department of Biomedicine, School of Life Sciences, Indonesia International Institute for Life Sciences, Jl. Pulomas Barat Kav 88, Jakarta 13210, Indonesia. FAU - Agustriawan, David AU - Agustriawan D AUID- ORCID: 0000-0003-1185-1145 AD - Department of Bioinformatics, School of Life Sciences, Indonesia International Institute for Life Sciences, Jl. Pulomas Barat Kav 88, Jakarta 13210, Indonesia. FAU - Andarini, Sita AU - Andarini S AD - Department of Pulmonology and Respiratory Medicine, Faculty of Medicine University of Indonesia, Persahabatan Hospital, Jl Persahabatan Raya 1, Jakarta 13230, Indonesia. LA - eng GR - 356/E4.1/AK.04.PT/202/Kementerian Pendidikan, Kebudayaan, Riset, dan Teknologi Republik Indonesia (Ministry of Education, Culture, Research and Technology, Republic of Indonesia), Southeast Asia Joint Funding Scheme for Research Innovation/ PT - Journal Article DEP - 20211209 PL - Switzerland TA - Vaccines (Basel) JT - Vaccines JID - 101629355 PMC - PMC8704007 OTO - NOTNLM OT - HLA-A*24:07 OT - SARS-CoV-2 OT - T-cell epitopes OT - cytotoxic T-cells OT - helper T-cells OT - human leukocyte antigen OT - immunoinformatics OT - multi-epitope peptide-based vaccine COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2021/12/29 06:00 MHDA- 2021/12/29 06:01 PMCR- 2021/12/09 CRDT- 2021/12/28 01:06 PHST- 2021/11/03 00:00 [received] PHST- 2021/11/28 00:00 [revised] PHST- 2021/11/30 00:00 [accepted] PHST- 2021/12/28 01:06 [entrez] PHST- 2021/12/29 06:00 [pubmed] PHST- 2021/12/29 06:01 [medline] PHST- 2021/12/09 00:00 [pmc-release] AID - vaccines9121459 [pii] AID - vaccines-09-01459 [pii] AID - 10.3390/vaccines9121459 [doi] PST - epublish SO - Vaccines (Basel). 2021 Dec 9;9(12):1459. doi: 10.3390/vaccines9121459.