Translating genomic sequences into antibody efficacy and safety against influenza toward clinical trial outcomes: a case study

Antibodies (Abs) are regarded as a newly emerging form of therapeutics that can provide passive protection against influenza. Although the application of genomics in clinics has increased dramatically, the number of therapeutics available for the treatment of many diseases remains insufficient. To translate genomics into medicines, we established a computational workflow to reconstruct 3D structures of hemagglutinin [HA, antigen (Ag)] and Ab for modeling Ab–HA interactions, based on their protein sequences. This platform was capable of testing the validity of bioinformatics predictions against viral neutralization titers for four Abs: CH65, CR8020, C05, and 5J8. By considering off-target effects, CR8020, the only successful candidate in clinical trials, was prospectively identified. Our approach could facilitate the discovery of Ab drugs against infectious diseases.