Identification of highly conserved surface-exposed peptides of spike protein for multiepitope vaccine design against emerging omicron variants: An immunoinformatic approach

Abstract

The COVID-19 pandemic, originating in Wuhan in 2019, was caused by SARS-CoV-2, leading to significant global fatalities. Despite the development of vaccines, the virus mutates, creating variants that evade vaccine-induced immunity. To address SARS-CoV-2′s evolving nature, a multiepitope vaccine was developed using immunoinformatics approach, specifically targeting the Omicron variant’s spike protein. This vaccine includes six CD8 + and eleven CD4 + epitopes selected for their immunogenicity, non-toxicity, and significant conservation among former Variants of Concern (VOCs) and Variants of Interest (VOIs), such as Alpha, Beta, Gamma, Delta, Lambda, Mu, R1, and Zeta, as well as current Variants Under Monitoring (VUMs) like XBB.1.5, XBB.1.16, EG.5, BA.2.86, and JN.1. Notably, certain epitopes like ELLHAPATV and PYRVVVLSFELLHAP were fully conserved across all tested variants in the spike protein’s receptor binding domain (RBD). Others, such as NATRFASVYAWNRKR, were fully conserved in all former VOCs and VOIs and 93.33 % in current VUMs, while ERDISTEIYQAGNKP was entirely conserved in current VUMs within the RBD region. The study went on to model, refine, and validate the vaccine prototype’s tertiary structure. Docking experiments and molecular dynamic simulations revealed robust and stable interactions with Toll-like receptor 4. Cloning and codon optimization confirmed successful expression in E. coli. Subsequently, the immunological reaction of the multiepitope vaccine demonstrated that the three-time administration of the prototype significantly enhanced the antibody response while decreasing the number of antigens. The designed vaccine’s epitopes showed significant combined global population coverage of 100 % with 89.75 % for CD8 + and 99.98 % for CD4 + epitopes and conservation across SARS-CoV-2 variants especially in current monitoring omicron subvariants, supporting its broader applicability and potential efficacy. Although, this promising vaccine candidate needs to undergo clinical trials to determine its effectiveness in neutralising SARS-CoV-2.