Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion

J Infect Dis. 2011 Dec 1;204(11):1692-701. doi: 10.1093/infdis/jir622. Epub 2011 Oct 12.

Abstract

Despite the medical importance of respiratory syncytial virus (RSV) infections, there is no vaccine or therapeutic agent available. Prophylactic administration of palivizumab, a humanized monoclonal RSV fusion (F) protein-specific antibody, can protect high-risk children. Previously, we have demonstrated that RSV can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the RSV protein F (F-VHHb nanobodies). Here, we investigated the mechanism by which these nanobodies neutralize RSV and tested their antiviral activity in vivo. We demonstrate that bivalent RSV F-specific nanobodies neutralize RSV infection by inhibiting fusion without affecting viral attachment. The ability of RSV F-specific nanobodies to protect against RSV infection was investigated in vivo. Intranasal administration of bivalent RSV F-specific nanobodies protected BALB/c mice from RSV infection, and associated pulmonary inflammation. Moreover, therapeutic treatment with these nanobodies after RSV infection could reduce viral replication and reduced pulmonary inflammation. Thus, nanobodies are promising therapeutic molecules for treatment of RSV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology*
  • Antiviral Agents / immunology
  • Antiviral Agents / pharmacology
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Respiratory Syncytial Virus Infections / drug therapy
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Viruses / immunology*
  • Time Factors
  • Viral Fusion Proteins / immunology
  • Viral Load / drug effects
  • Virus Attachment / drug effects*
  • Virus Internalization / drug effects*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antiviral Agents
  • Viral Fusion Proteins