Design of a Novel Recombinant Protein Vaccine Based on BA.4 and BA.5 subvariants of SARS-CoV-2: An immunoinformatic and structural approach

Abstract Currently, many efforts have been made against Coronavirus 2019 (COVID-19) as a global outbreak. So far, several vaccines with different platforms are available in the market. Various variants of the SAR-CoV-2 virus have evolved over time. The emergence of variant of Concerns (VOCs), especially new subvariants of BA.4 and BA.5, which can neutralize the effect of current vaccines. Therefore, in this study, we used the bioinformatics approach to design an effective novel candidate vaccine against Variant of Concern (VOC) of COVID-19 (B.1.1.529 or Omicron) based on Spike (S1_ receptor-binding domain or RBD) protein sequence. Here, we employed bioinformatics tools to design a novel fusion protein construct containing the mutant sequence of Omicron Spike_S1_RBD region (as target antigen) and amino acid sequence of human β-defensin-2 as adjuvant molecule. Then, the mutant RBD and β-defensin-2 amino acid sequences were joined together by the suitable linker and novel vaccine construct was designed. Subsequently, immunological and structural evaluations such as antigenicity, allergenicity, physicochemical properties, 3D modeling, molecular docking, and fast flexibility simulations, immune responses simulation as well as in silico cloning were performed. Immunological and structural computational data showed that designed vaccine construct potentially has proper capacity for inducing immune responses against BA.4/5 subvariant of Omicron. Based on the preliminary results, in vitro and in vivo experiments are required for validation in the future.