A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein

Nat Commun. 2019 Sep 12;10(1):4153. doi: 10.1038/s41467-019-12137-1.

Abstract

Respiratory syncytial virus (RSV) infection is the leading cause of hospitalization and infant mortality under six months of age worldwide; therefore, the prevention of RSV infection in all infants represents a significant unmet medical need. Here we report the isolation of a potent and broadly neutralizing RSV monoclonal antibody derived from a human memory B-cell. This antibody, RB1, is equipotent on RSV A and B subtypes, potently neutralizes a diverse panel of clinical isolates in vitro and demonstrates in vivo protection. It binds to a highly conserved epitope in antigenic site IV of the RSV fusion glycoprotein. RB1 is the parental antibody to MK-1654 which is currently in clinical development for the prevention of RSV infection in infants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Viral / immunology*
  • B-Lymphocytes / immunology
  • Binding Sites
  • Broadly Neutralizing Antibodies / immunology*
  • Conserved Sequence*
  • Disease Models, Animal
  • Epitopes / immunology
  • Female
  • Glycoproteins / immunology*
  • Humans
  • Immunologic Memory
  • Models, Molecular
  • Protein Binding
  • Respiratory Syncytial Virus, Human / immunology*
  • Sigmodontinae
  • Viral Fusion Proteins / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Broadly Neutralizing Antibodies
  • Epitopes
  • Glycoproteins
  • Viral Fusion Proteins