Computational Design of a Novel Candidate Multi-Epitope Vaccine to Boost Immune Responses against SARS‐COV‐2

Abstract

Background: The fast development of an effective vaccine is the major demand for protection against the SARS-COV-2 virus outbreak. Immuno-informatics tools are time-saving and cost-effective methods to hasten the design and establishment of a proficient multi-peptide candidate vaccine. The utilization of multi-epitope-based vaccines has demonstrated to be a promising immunization approach against viruses due to the induction of long-term protective immunity. Method: In the present study, a complete computational approach was conducted to design a multi-epitope-based vaccine composed of cytotoxic T lymphocyte and helper T lymphocyte epitopes of Spike and Nucleocapsid proteins conserved regions. The potential viral peptides as the candidate vaccine were screened regarding convenient features like hydrophilicity, flexibility, antigenicity, and charged properties. In the next step, the vaccine efficacy needed to be improved by an immune adjuvant. For this purpose, the C-terminal domain of heat shock protein gp96 (CT-GP96) was applied as a potent adjuvant for enhancing immunity. The final assembled construct was fused with the assistance of suitable linkers and cloned in a pET28a expression vector for overproduction of the vaccine in a bacterial host. Result: Following validation of the final construct in terms of its efficacy, stability, and exposure ability, molecular docking analysis was carried out to reveal its interaction with toll-like receptor 4, which is required to trigger the immune response. The molecular simulations by iMODS software confirmed the stability of the binding interface. Additionally, the computational cloning of the assembled vaccine in pET28a plasmid showed the possibility of producing a vaccine construct post-transformation in an E. coli host. Conclusion: The computational analysis indicated that this construct could be a potent prophylactic and therapeutic multi-epitope vaccine candidate against SARS‐COV‐2 once its effectiveness is verified by experimental and animal studies.