Exploration of surface glycoprotein to design multi-epitope vaccine for the prevention of Covid-19

Abstract

Stimulation and generation of T and B cell mediated long-term immune response is essential for the curbing of a deadly virus such as SAR-CoV-2. Immunoinformatics approach in vaccine design takes advantage of antigenic and non-allergenic epitopes present on the spike glycoprotein of SARS-CoV-2 to elicit immune responses. T cells and B cells epitopes were predicted, and the selected residues were subjected to allergenicity, antigenicity and toxicity screening which were linked by appropriate linkers to form a multi-epitope subunit vaccine. The physiochemical properties of the vaccine construct was analyzed and the molecular weight, molecular formula, theoretical isoelectric point value, half-life, solubility score, instability index, aliphatic index and GRAVY were predicted. The vaccine structure was constructed, refined, validated, and disulfide engineered to get the best model. Molecular binding simulation and molecular dynamics simulation were carried out to predict the stability and binding affinity of the vaccine construct with TLRs. Codon acclimatization and in silico cloning were performed to confirm the vaccine expression and potency. Results obtained indicated that this novel vaccine candidate is non-toxic, capable of initiating the immunogenic response and will not induce an allergic reaction. The highest binding energy was observed in TLR 4 (-1398.1) and the least is TLR 2 (-1479. 6). The steady rise in Th (helper) cell population with memory development was noticed and IFN-g was provoked after simulation. At this point, the vaccine candidate awaits animal trial to validate its efficacy and safety for use in the prevention of the novel COVID-19 infections.

COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing Hyperinflammation

“…Although this was designed, and multiple amino acids from the 3 epitopes in the NOM protein are contributing to the binding to TLR4, it shows that components of SARS-COV-2 are binding well to TLR4 and raises further questions. More recently, several other in silico studies have designed multiepitope vaccines using SARS-CoV-2 spike glycoprotein constructs/subunits, and they are found to bind TLR4 using molecular docking studies (see [ 115 – 119 ]).…”

Computational construction of a glycoprotein multi-epitope subunit vaccine candidate for old and new South-African SARS-CoV-2 virus strains

“…6 a and b), and 83.871% score was revealed by ERRAT online server. The following previously published scientific research papers adopted this method for validation [ 23 , 28 , 30 , 93 ].

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“…Many scientific literatures have adopted the knowledge of computational genomics and immunoinformatic to proffer solutions to different diseases [ [85] , [86] , [87] ]. Many pieces of scientific literature have been published on the computational design of glycoprotein multi-epitope subunit vaccine candidates [ [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ], but none has been specifically focused yet on the computational design of vaccine candidate for the old and new variants of the entire South African SARS-CoV-2 virus data strains from the year 2020–2021 [ [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ]. Our preference for adopting a spike-like glycoprotein as a potential choice for vaccine design is due to its capacity to produce vaccine candidates that are potent, efficacious, effective, and characterized by the absence of allergic reactions.…”

Designing a conserved peptide-based subunit vaccine against SARS-CoV-2 using immunoinformatics approach

“…Nucleotide sequences were recovered from the GISAID database (accession information in Supplementary Table 1) and the B-cell, HTL and CTL epitopes were projected (Table 1 ). Stimulation and generation of T and B cell-mediated long-term immune response are essential for the curbing of a deadly virus such as SAR-CoV-2 (Oladipo et al 2020a , b ). B-cells are responsible for antibody maintenance and facilitate response to future exposure to an antigen (Tobón et al 2013 ).…”

“…The Coronavirus (COVID-19) has been established to be caused by severe acute respiratory syndrome virus known as SARS-CoV-2 (Dagur and Dhakar 2020 ). SARS-CoV-2 is similar to the severe acute respiratory syndrome virus (SARS-CoV) by ~ 80%, also has ~ 50% similarity to the Middle East respiratory syndrome virus (MERS-CoV) and ~ 96% closeness to bat coronavirus (RaTG13) (Oladipo et al 2020a , b ). SARS-CoV-2 is a member of betacoronavirus, a positive polar single-stranded RNA genome, like MERS-CoV and SARS-CoV.…”