Predicting the antigenic evolution of SARS-COV-2 with deep learning

The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) antigenic profile evolves in response to the vaccine and natural infection-derived immune pressure, resulting in immune escape and threatening public health. Exploring the possible antigenic evolutionary potentials improves public health preparedness, but it is limited by the lack of experimental assays as the sequence space is exponentially large. Here we introduce the Machine Learning-guided Antigenic Evolution Prediction (MLAEP), which combines structure modeling, multi-task learning, and genetic algorithm to model the viral fitness landscape and explore the antigenic evolution via in silico directed evolution. As demonstrated by existing SARS-COV-2 variants, MLAEP can infer the order of variants along antigenic evolutionary trajectories, which is also strongly correlated with their sampling time. The novel mutations predicted by MLAEP are also found in immunocompromised covid patients and newly emerging variants, like XBB1.5. The predictions of MLAEP were validated by conducting in vitro neutralizing antibody binding assay, which demonstrated that the model-generated variants displayed significantly increased immune evasion ability compared with the controls. In sum, our approach enables profiling existing variants and forecasting prospective antigenic variants, thus may help guide the development of vaccines and increase preparedness against future variants. Our model is available at https://mlaep.cbrc.kaust.edu.sa.