Prediction and mitigation of mutation threats to COVID-19 vaccines and antibody therapies.

Chen, Jiahui; Gao, Kaifu; Wang, Rui; Wei, Guowei

Antibody therapeutics and vaccines are among our last resort to end the raging COVID-19 pandemic.They, however, are prone to over 1,800 mutations uncovered by a Mutation Tracker. It is urgent to understand how vaccines and antibodies in the development would be impacted by mutations. In this work, we first study the mechanism, frequency, and ratio of mutations on the spike (S) protein, which is the common target of most COVID-19 vaccines and antibody therapies. Additionally, we build a library of antibody structures and analyze their 2D and 3D characteristics. Moreover, we predict the mutation-induced binding free energy (BFE) changes for the complexes of S protein and antibodies or ACE2. By integrating genetics, biophysics, deep learning, and algebraic topology, we deduce that some of the mutations such as M153I, S254F, and S255F may weaken the binding of S protein and antibodies, and potentially disrupt the efficacy and reliability of antibody therapies and vaccines in the development. We provide a strategy to prioritize the selection of mutations for designing vaccines or antibody cocktails.