A conserved subunit vaccine designed against SARS-CoV-2 variants showed evidence in neutralizing the virus.

Novel coronavirus (SARS-CoV-2) leads to coronavirus disease 19 (COVID-19), declared as a pandemic that outbreaks within almost 225 countries worldwide. For the time being, numerous mutations have been reported that led to the generation of numerous variants spread more rapidly. This study aims to establish an efficient multi-epitope subunit vaccine that could elicit both T-cell and B-cell responses sufficient to recognize three confirmed surface proteins of the virus. The sequences of the viral surface proteins, e.g., an envelope protein (E), membrane glycoprotein (M), and S1 and S2 domain of spike surface glycoprotein (S), were analyzed by an immunoinformatic approach. Top immunogenic epitopes have been selected based on the assessment of the affinity with MHC class-I and MHC class-II, population coverage, along with conservancy among wild type and new variants of SARS-CoV-2 genomes. Molecular docking and molecular dynamic simulation suggest that the proposed top peptides have the potential to interact with the highest number of both the MHC class I and MHC class II. The epitopes were assembled by the appropriate linkers to form a multi-epitope vaccine. Epitopes used in the vaccine construct are conserved in all the variants evolved till now. This in silico-designed multi-epitope vaccine is highly immunogenic and induces levels of SARS-CoV2-neutralizing antibodies in mice, which is detected by inhibition of cytopathic effect in Vero cell monolayer. Further studies are required to improve its efficiency in the prevention of virus replication in lung tissue, in addition to safety validation as a step for human application to combat SARS-CoV-2 variants. KEY POINTS: • We discovered five T-cell epitopes from three surface proteins of SARS-CoV-2. • These are conserved in the wild-type virus and variants, e.g., beta, delta, and omicron. • The multi-epitope vaccine can induce IgG in mice that can neutralize the virus.