Design of multi-epitope vaccine candidate against SARS-CoV-2: a in-silico study

Abstract

The best therapeutic strategy to find an effective vaccine against SARS-CoV-2 is to explore the target structural protein. In the present study, a novel multi-epitope vaccine is designed using in silico tools that potentially trigger both CD4 and CD8 T-cell immune responses against the novel Coronavirus. The vaccine candidate was designed using B and T-cell epitopes that can act as an immunogen and elicits immune response in the host system. NCBI was used for the retrieval of surface spike glycoprotein, of novel corona virus (SARS-CoV-2) strains. VaxiJen server screens the most important immunogen of all the proteins and IEDB server gives the prediction and analysis of B and T cell epitopes. Final vaccine construct was designed in silico composed of 425 amino acids including the 50S ribosomal protein adjuvant and the construct was computationally validated in terms of antigenicity, allergenicity and stability on considering all critical parameters into consideration. The results subjected to the modeling and docking studies of vaccine were validated. Molecular docking study revealed the protein-protein binding interactions between the vaccine construct and TLR-3 immune receptor. The MD simulations confirmed stability of the binding pose. The immune simulation results showed significant response for immune cells. The findings of the study confirmed that the final vaccine construct of chimeric peptide could able to enhance the immune response against nCoV-19.

Keywords: COVID-19; IEDB; Vaxigen; immuno-informatics; spike glycoprotein; vaccine design.

Figure 1.

(a) Ramachandran plot is showing 99% of the residues are in favorable region; (b) ProSA-web z-score determined by X-ray crystallography (light blue) and NMR spectroscopy (dark blue) according to the length.

Figure 2.

(a) Secondary structure predictions of vaccine construct using PSIPRED and (b) Solubility analysis vaccine construct using ProtSol.

Figure 3.

AllerTOP 2.0 predicted the vaccine construct is a non allergen.

Figure 4.

Cloning of the final vaccine construct into the pET28a (+) expression vector and purple represents the gene coding vaccine DNA sequence.

Figure 5.

(a) Homology modeling of vaccine construct generated by I-TASSER; (b) Docking complex of TLR-3 (PDB ID: 1ziw) and vaccine construct; (c) Docking complex of TLR-3 and vaccine construct interactions visualized using DIMPLOT (Ligplus 1.2 version) (chain A- TLR-3 protein; chain B – Vaccine construct).

Figure 6.

The RMSD values of simulated complex of the TLR-3 and Vaccine construct.

Figure 7.

C-ImmSim server prediction results of immune response after administering vaccine construct; (a) Antigen and immunoglobulins; (b) B-lymphocytes cell population; (c) CD4⁺ helper T cells population per state; (d) Induced levels of the cytokine and Simpson index, D.