Effects of K444T, N460K, F490S, L452R, and T478R Mutations on the Solubility, Allergenicity, and Immunogenicity of SARS-CoV-2-based Spike Protein Vaccines

The spike glycoprotein is a prime focal point for vaccine development due to its possession of numerous T-cell and B-cell epitopes. In this study, we investigated the effects of some important mutations (K444T, N460K, F490S, L452R, and T478R) on the immunogenicity of the spike protein in the Omicron variant. Additionally, we forecasted the effects of these mutations on the spike protein’s solubility, allergenicity, and immunogenicity.

In this research, we obtained 100 SARS-CoV-2 spike sequences from two databases, namely the Global Initiative on Sharing All Influenza Data (GISAID) EpiCoV and NCBI. We conducted a comparative analysis between the wild-type spike protein (Wuhan accession number: NC_045512.2) and the mutated spike proteins. The analysis focused on solubility, allergenicity, and immunogenicity. It was carried out using various bioinformatics servers, such as Dynamut, toxin pred, soluprot, Allertop, IEDB, and Vaxigen, as well as tools, like Mega XI and Pymol II.V.II visualizer.

According to the prediction of the IEDB server, the K444T mutation is likely to decrease the humoral immune response. In addition, spike proteins in wild types and mutants do not have allergenic properties, and these proteins are soluble and can be expressed in Escherichia coli.

Vaccines formulated using spike protein design are effective. These findings indicate the potential for developing pan-coronavirus vaccines that offer protection not only against SARS-CoV-2 but also against a range of other coronaviruses in the future.