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

PLoS One. 2016 Jun 3;11(6):e0156798. doi: 10.1371/journal.pone.0156798. eCollection 2016.

Abstract

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.

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / therapeutic use*
  • Antibodies, Viral / immunology
  • Antibodies, Viral / therapeutic use*
  • Cell Surface Display Techniques
  • Epitope Mapping
  • Epitopes / immunology
  • Glycoproteins / immunology*
  • Humans
  • 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*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Glycoproteins
  • Respiratory Syncytial Virus Vaccines

Grants and funding

The research was fully funded by Merck and Co., Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.