Abstract
Coronaviruses (CoVs) cause diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19). Therefore, this study was conducted to combat major CoVs via a trivalent subunit vaccine, which was engineered by implementing sequences of spike (S) protein, nucleocapsid (N), envelope (E), membrane (M) protein, non-structural protein (nsp) 3, and nsp8 antigens. The CTL, HTL, MHC I, and IFN-γ epitopes were predicted via CTLPRED, IEDB, and IFN epitope servers, respectively. Also, to stimulate strong helper T lymphocytes (HTLs) responses, Pan HLA DR-binding epitope (PADRE) was used. Also, for boosting the immune response, β-defensin 2 was added to the construct as an adjuvant. Furthermore, TAT was applied to the vaccine to facilitate the intracellular delivery. Finally, TAT, adjuvant, PADRE, and selected epitopes were appropriately assembled. Based on the predicted epitopes, a trivalent multi-epitope vaccine with a molecular weight of 74.8 kDa was constructed. Further analyses predicted the molecule to be a strong antigen, and a non-allergenic and soluble protein. Secondary and tertiary structures were predicted. Additionally, analyses validated the stability of the proposed vaccine. Molecular docking and molecular dynamics simulation (MDS) showed binding affinity and stability of the vaccine-TLR3 complex was favorable. The predicted epitopes demonstrated a strong potential to stimulate T and B-cell mediated immune responses. Furthermore, codon optimization and in silico cloning guaranteed increased expression. In summary, investigations demonstrated that this next-generation approach might provide a new horizon for the development of a highly immunogenic vaccine against SARS‐CoV, MERS‐CoV, and SARS-CoV-2.
Communicated by Ramaswamy H. Sarma
Graphical Abstract
![](/cms/asset/93b54515-6bde-431c-b85d-c28c1caf488a/tbsd_a_1876774_uf0001_c.jpg)
Acknowledgements
We thank Student Research Committee, Babol University of Medical Sciences, and all staff at Immunoregulation Research Center, Health Research Institute, Babol University of Medical Sciences.
Disclosure statement
No potential conflict of interest was reported by the authors.
Availability of data and materials
All data and materials of this work are available from the corresponding author on reasonable request.
Authors’ contributions
A.R., M.B., K.S., S.M., and H.R.N. conceptualized the study and prepared the initial draft. MD simulations and visualized results conducted by K.S. H.R.N. supervised the project, critically appraised the manuscript, and prepared the final draft