An immunoinformatics approach in designing high-coverage mRNA multi-epitope vaccine against multivariant SARS-CoV-2.

BACKGROUND

Despite the decreasing cases, SARS-CoV-2, with its endemic status, still threatens public health, and developing a variant-proof vaccine could be a promising strategy to prevent future infection. In this study, utilizing immunoinformatics and reverse vaccinology, we aimed to develop a multi-epitope mRNA vaccine with high population coverage, targeting multiple variants of SARS-CoV-2.

METHODS

To design a multivariant vaccine, 20,567 sequences consisting of all SARS-CoV-2's variants of concern whole genome were retrieved. Utilizing an immunoinformatics approach, the selected antigens spike and nucleocapsid proteins were analyzed to predict linear B lymphocyte (LBL), helper T lymphocyte (HTL), and cytotoxic T lymphocyte (CTL) epitopes. These epitopes were evaluated based on antigenicity, toxicity, allergenicity, conservancy, and coverage at both global and Indonesian levels. The identified epitopes were further subjected to molecular docking analysis with MHC molecules and combined into the design of a multi-epitope vaccine. The validated 3D structure of the vaccine construct (VC) was used in molecular docking with TLR4 and BCR. The vaccine construct's potential in eliciting immune responses was also assessed.

RESULTS

The predicted epitopes demonstrated extensive population coverage, encompassing 99.99% of the global population and 99.39% of the Indonesian population, respectively. The selected epitopes consisted of four LBL, five HTL, and three CTL epitopes were combined using linkers to make a multi-epitope construct, which was antigenic, non-allergenic, 257 amino acids long, and most of the structure was coil (61.87%). Furthermore, molecular docking analysis revealed potent interactions between the validated 3D structure and the TLR4 and BCR receptors, while molecular dynamic simulations confirmed the stability of the VC-TLR4 and VC-BCR complexes. Additionally, mRNA codon optimization was performed to enhance vaccine expression efficiency, and secondary structure analysis indicated that the designed mRNA vaccine possessed a stable conformation.

CONCLUSION

As a result, an mRNA vaccine candidate was obtained with high population coverage and could induce a robust and protective immune response against multiple variants of SARS-CoV-2. Therefore, further studies are required to validate the safety and efficacy of the proposed vaccine candidate.