SARS-CoV-2 Lambda and Omicron Variants: Antigenicity Evaluation of Spike Proteins as Potential Targets for Vaccine Development

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide as an Omicron variant (B.1.1.529). Compared with the original SARS-CoV-2, this variant has more than 30 mutations on its spike. The Lambda variant (known as SARS-CoV-2 lineage C.37) is another variant of interest. The Lambda spike protein bears seven mutations; G75V, T76I, L452Q, F490S, D614G, T859N, and ∆247-253. The effect of such mutations on immune escape from neutralizing antibodies and infectivity is unknown.

In-silico tools were applied to predict the antigenicity of the spikes of Lambda and Omicron variants and the results were compared to the reference Wuhan spike protein antigenicity. SWISS-MODEL, MolProbity, and QMEAN were used for model quality assessment. DiscoTope2.0, BEpro, and Ellipro were used for the prediction of conformational and linear B cell epitopes.

The evaluation of the obtained modeled proteins showed that the predicted models by Swiss-Model had higher quality for Lambda and Omicron spikes with 0.56% and 1.63% of residues in outlier and 94.39% and 92.51% residues in favored regions, respectively. The results of conformational B cell epitope prediction showed 6 epitopic regions on S1 of Lambda spike and 1 epitopic region on the S2 segment of the protein. For the Omicron variant, 9 epitopic regions existed on S1 and 1 epitopic region (1137-1159) was on S2.

Our results suggested that B cell epitope removal and reducing the antigenicity properties of the epitopic residues involve reducing susceptibility to antibody neutralization of the mutant protein