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.
Institute of Medical Informatics, Department of Computer Science and Information Engineering, National Cheng Kung University, Taiwan; Institute of Oral Medicine, National Cheng Kung University College of Medicine, Taiwan. Electronic address: yanghsi@mail.ncku.edu.tw.
Hsih-Te
HT
Yang
Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Hong
H
Yang
Institute of Medical Informatics, Department of Computer Science and Information Engineering, National Cheng Kung University, Taiwan.
Jung-Hsien
JH
Chiang
Department of Bioscience Technology, Chang Jung Christian University, Taiwan.
Shih-Jon
SJ
Wang
D000906:Antibodies / Q000737:chemistry / Q000627:therapeutic use*; D019295:Computational Biology; D023281:Genomics; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*; D062105:Molecular Docking Simulation
D000906:Antibodies