Deep survey for designing a vaccine against SARS-CoV-2 and its new mutations

Abstract

The ongoing global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has prompted worldwide vaccine development. Several vaccines have been authorized by WHO, FDA, or MOH of different countries. However, issues such as need for cold chain, price, and most importantly access problems have limited vaccine usage in some nations especially developing countries. Moreover, the vast global demand justifies further attempts for vaccine development. Multi-epitope polypeptide vaccines enjoy several key features including safety and lower production and transfer costs and could be designed by in silico tools. Spike protein (S), membrane protein (M), and nucleocapsid protein (N), the three major structural proteins of SARS-CoV-2, are ideal candidates for epitope selection. ORF3a (open reading frame3a), a transmembrane protein with pro-apoptotic functions, could be another proper target. Thus, a novel multi-epitope vaccine against SARS-CoV-2 was designed using these four proteins and LL37, a TLR3 agonist adjuvant, through different immunoinformatics and bioinformatics tools. The proposed multi-epitope vaccine is expected to induce robust humoral and cellular immune responses against SARS-CoV-2 with a population coverage of 76.92 % due to containing different immunodominant epitopes and LL37 adjuvant. Selecting epitopes derived from one functional and three structural proteins suggests the protective ability of the vaccine irrespective of probable virus mutations. The computationally observed proper interaction of LL37 with TLR3 implies its ability to induce immune responses effectively. Besides, it showed acceptable structural and physicochemical properties. The in-silico cloning results predicted its high efficiency production in Escherichia coli. Future experimental studies could further confirm its immunological efficacy.