Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2

Ehling, R. A.; Minot, M.; Overath, M. D.; Sheward, D. J.; Han, J.; Gao, B.; Taft, J. M.; Pertseva, M.; Weber, C. R.; Frei, L.; Bikias, T.; Murrell, B.; Reddy, S. T.

doi:10.1101/2024.03.28.587189

bioRxiv · 10.1101/2024.03.28.587189

Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2

Ehling, R. A.·Minot, M.·Overath, M. D.·Sheward, D. J.·Han, J.·Gao, B.·Taft, J. M.·Pertseva, M.·Weber, C. R.·Frei, L.·Bikias, T.·Murrell, B.·Reddy, S. T.

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Abstract

The Covid-19 pandemic showcases a coevolutionary race between the human immune system and SARS-CoV-2, mirroring the Red Queen hypothesis of evolutionary biology. The immune system generates neutralizing antibodies targeting the SARS-CoV-2 spike proteins receptor binding domain (RBD), crucial for host cell invasion, while the virus evolves to evade antibody recognition. Here, we establish a synthetic coevolution system combining high-throughput screening of antibody and RBD variant libraries with protein mutagenesis, surface display, and deep sequencing. Additionally, we train a protein language machine learning model that predicts antibody escape to RBD variants. Synthetic coevolution reveals antagonistic and compensatory mutational trajectories of neutralizing antibodies and SARS-CoV-2 variants, enhancing the understanding of this evolutionary conflict.

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Ehling, R. A., Minot, M., Overath, M. D., Sheward, D. J., Han, J., Gao, B., Taft, J. M., Pertseva, M., Weber, C. R., Frei, L., Bikias, T., Murrell, B., Reddy, S. T.. 2024-04-01. Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2. https://doi.org/10.1101/2024.03.28.587189

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