A Next-Generation Vaccine Candidate Using Alternative Epitopes to Protect against Wuhan and All Significant Mutant Variants of SARS-CoV-2: An Immunoinformatics Approach.

ABSTRACT

Newly emerging significant SARS-CoV-2 variants such as B.1.1.7, B.1.351, and B.1.1.28 are the variant of concern (VOC) for the human race. These variants are getting challenging to contain from spreading worldwide. Because of these variants, the second wave has started in various countries and is threatening human civilization. Thus, we require efficient vaccines that can combat all emerging variants of SARS-CoV-2. Therefore, we took the initiative to develop a peptide-based next-generation vaccine using four variants (Wuhan variant, B.1.1.7, B.1.351, and B.1.1.28) that could potentially combat SARS-CoV-2 variants. We applied a series of computational tools, servers, and software to identify the most significant epitopes present on the mutagenic regions of SARS-CoV-2 variants. The immunoinformatics approaches were used to identify common B cell derived T cell epitopes, influencing the host immune system. Consequently, to develop a novel vaccine candidate, the antigenic epitopes were linked with a flexible and stable peptide linker, and the adjuvant was added at the N-terminal end. 3D vaccine candidate structure was refined, and quality was assessed using web servers. The physicochemical properties and safety parameters of the vaccine construct were assessed through bioinformatics and immunoinformatics tools. The molecular docking analysis between TLR4/MD2 and the proposed vaccine candidate demonstrated a satisfactory interaction. The molecular dynamics studies confirmed the stability of the vaccine candidate. Finally, we optimized the proposed vaccine through codon optimization and in silico cloning to study the expression. Our multi-epitopic next-generation peptide vaccine construct can boost immunity against the Wuhan variant and all significant mutant variants of SARS-CoV-2.