Structure basis of neutralization by a novel site II/IV antibody against respiratory syncytial virus fusion protein

PLoS One. 2019 Feb 7;14(2):e0210749. doi: 10.1371/journal.pone.0210749. eCollection 2019.


Globally, human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in newborns, young children, and the elderly for which there is no vaccine. The RSV fusion (F) glycoprotein is a major target for vaccine development. Here, we describe a novel monoclonal antibody (designated as R4.C6) that recognizes both pre-fusion and post-fusion RSV F, and binds with nanomole affinity to a unique neutralizing site comprised of antigenic sites II and IV on the globular head. A 3.9 Å-resolution structure of RSV F-R4.C6 Fab complex was obtained by single particle cryo-electron microscopy and 3D reconstruction. The structure unraveled detailed interactions of R4.C6 with antigenic site II on one protomer and site IV on a neighboring protomer of post-fusion RSV F protein. These findings significantly further our understanding of the antigenic complexity of the F protein and provide new insights into RSV vaccine design.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / chemistry*
  • Antibodies, Viral / immunology
  • Binding Sites, Antibody*
  • Cell Line
  • Humans
  • Immunoglobulin Fab Fragments / chemistry*
  • Immunoglobulin Fab Fragments / immunology
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Viruses / chemistry*
  • Respiratory Syncytial Viruses / immunology
  • Spodoptera
  • Viral Fusion Proteins / chemistry*
  • Viral Fusion Proteins / immunology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin Fab Fragments
  • Viral Fusion Proteins