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

Abstract

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. Supplementary Information The online version contains supplementary material available at 10.1007/s00253-022-11988-x.

Significance of Conserved Regions in Coronavirus Spike Protein for Developing a Novel Vaccine against SARS-CoV-2 Infection

“…A recent immunoinformatic study predicted conserved and highly immunogenic CTL-induced epitopes on S1 VRFPNITNL (327–335 aa) and PYRVVVLSF (507–515 aa) ( Table 1 ), while the CTL-induced epitopes on S2 were identified to be VVFLHVTYV (1060–1068 aa) and GVVFLHVTY (1059–1067 aa) ( Table 2 ) [ 117 ]. Based on the conservancy, antigenicity, allergenicity, population coverage and transmembrane location, another study chose potential conserved epitopes from the S1 (FNATRFASVYAWNRK, 342–356 aa) ( Table 1 ), S2 (FLHVTYVPAQEKNFT, 1062–1072 aa) ( Table 2 ) and the E/M protein to construct a SARS-CoV-2 vaccine and revealed that it had high immunogenicity and broad neutralizing activity against the SARS-CoV-2 RBD ( Figure 3 ) [ 118 ]. Jiang et al, with web-based analytic tools, also predicted potential T cell epitopes induced by the SARS-CoV-2 SP and narrowed them down to CD4 or CD8 T cell epitopes using ELIspot and a cytolytic assay [ 119 ].…”

Investigation of the vaccine potential of an in silico designed FepA peptide vaccine against Shigella flexneri in mice model

“…The FepA protein (outer membrane protein) in Shigella is highly immunogenic [41] , [43] , with some modification and incomplete/complete adjuvant FepA hapten as a vaccine candidate tested on mice model to determine its immune responses against S. flexneri . Our previous study on multi-epitope-based synthetic vaccines also showed to produce neutralizing antibodies on Vero-2 cell culture against SARS-CoV-2 [42] .…”

Multi-epitopes vaccine design for surface glycoprotein against SARS-CoV-2 using immunoinformatic approach

“…3 e). Parker's hydrophobicity was used to identify hydrophobicity [ 49 ] the values which are −7.629 (minimum) and 7.743 (maximum). The average value was 1.34 ( Fig.…”