Discovery and Characterization of Phage Display-Derived Human Monoclonal Antibodies against RSV F Glycoprotein

• Published in: PloS one Vol. 11; no. 6; p. e0156798
• Main Authors: Chen, Zhifeng, Zhang, Lan, Tang, Aimin, Callahan, Cheryl, Pristatsky, Pavlo, Swoyer, Ryan, Cejas, Pedro, Nahas, Debbie, Galli, Jennifer, Cosmi, Scott, DiStefano, Daniel, Hoang, Van M., Bett, Andrew, Casimiro, Danilo, Vora, Kalpit A.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.06.2016; Public Library of Science (PLoS)
• Subjects: Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - therapeutic use; Antibodies, Viral - immunology; Antibodies, Viral - therapeutic use; Bacteriophages; Binding; Biology and Life Sciences; Cell Surface Display Techniques; Epitope Mapping; Epitopes - immunology; F protein; Geriatrics; Glycoproteins; Glycoproteins - immunology; Gold; Health aspects; Humans; Immunization; Immunoglobulins; Infants; Infections; Infectious diseases; Laboratories; Medicine and Health Sciences; Molecular biology; Monoclonal antibodies; Neutralizing; Older people; Panning; Phage display; Phages; Physical Sciences; Properties; Proteins; R&D; Research & development; Research and Analysis Methods; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Virus Vaccines - therapeutic use; Respiratory Syncytial Viruses - drug effects; Respiratory Syncytial Viruses - immunology; Respiratory Syncytial Viruses - pathogenicity; Respiratory tract; Respiratory tract diseases; Vaccines; Virology; Viruses; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0156798

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in infants, the elderly and in immunosuppressed populations. The vast majority of neutralizing antibodies isolated from human subjects target the RSV fusion (F) glycoprotein, making it an attractive target for the development of vaccines and therapeutic antibodies. Currently, Synagis® (palivizumab) is the only FDA approved antibody drug for the prevention of RSV infection, and there is a great need for more effective vaccines and therapeutics. Phage display is a powerful tool in antibody discovery with the advantage that it does not require samples from immunized subjects. In this study, Morphosys HuCAL GOLD® phage libraries were used for panning against RSV prefusion and postfusion F proteins. Panels of human monoclonal antibodies (mAbs) against RSV F protein were discovered following phage library panning and characterized. Antibodies binding specifically to prefusion or postfusion F proteins and those binding both conformations were identified. 3B1 is a prototypic postfusion F specific antibody while 2E1 is a prototypic prefusion F specific antibody. 2E1 is a potent broadly neutralizing antibody against both RSV A and B strains. Epitope mapping experiments identified a conformational epitope spanning across three discontinuous sections of the RSV F protein, as well as critical residues for antibody interaction.