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

Marsia Gustiananda, Bobby Prabowo Sulistyo, David Agustriawan, Sita Andarini

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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 peptide899WSMATYYLF907 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.

Original languageEnglish
Article number1459
JournalVaccines
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 2021

Keywords

  • Cytotoxic T-cells
  • Helper T-cells
  • HLA-A*24:07
  • Human leukocyte antigen
  • Immunoinformatics
  • Multi-epitope peptide-based vaccine
  • SARS-CoV-2
  • T-cell epitopes

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