SAS: A Platform of Spike Antigenicity for SARS-CoV-2

Since the outbreak of SARS-CoV-2, antigenicity concerns continue to linger with emerging mutants. As recent variants have shown decreased reactivity to previously determined monoclonal antibodies (mAbs) or sera, monitoring the antigenicity change of circulating mutants is urgently needed for vaccine effectiveness. Currently, antigenic comparison is mainly carried out by immuno-binding assays. Yet, an online predicting system is highly desirable to complement the targeted experimental tests from the perspective of time and cost. Here, we provided a platform of SAS (Spike protein Antigenicity for SARS-CoV-2), enabling predicting the resistant effect of emerging variants and the dynamic coverage of SARS-CoV-2 antibodies among circulating strains. When being compared to experimental results, SAS prediction obtained the consistency of 100% on 8 mAb-binding tests with detailed epitope covering mutational sites, and 80.3% on 223 anti-serum tests. Moreover, on the latest South Africa escaping strain (B.1.351), SAS predicted a significant resistance to reference strain at multiple mutated epitopes, agreeing well with the vaccine evaluation results. SAS enables auto-updating from GISAID, and the current version collects 867K GISAID strains, 15.4K unique spike (S) variants, and 28 validated and predicted epitope regions that include 339 antigenic sites. Together with the targeted immune-binding experiments, SAS may be helpful to reduce the experimental searching space, indicate the emergence and expansion of antigenic variants, and suggest the dynamic coverage of representative mAbs/vaccines among the latest circulating strains. SAS can be accessed at .

Automated summary

Since the outbreak of SARS-CoV-2, concerns regarding antigenicity have been persistent due to emerging mutants. A platform named SAS has been developed to predict the resistant effect of emerging variants and the dynamic coverage of SARS-CoV-2 antibodies among circulating strains, providing valuable insights for vaccine effectiveness and epidemiological strategies. The SAS prediction results have shown good consistency with experimental tests, offering a potential tool to complement targeted immune-binding experiments and track the emergence of antigenic variants.