Neutralizing human monoclonal antibodies to severe acute respiratory syndrome coronavirus: target, mechanism of action, and therapeutic potential

Rev Med Virol. 2012 Jan;22(1):2-17. doi: 10.1002/rmv.706. Epub 2011 Sep 8.

Abstract

The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) led to a rapid response not only to contain the outbreak but also to identify possible therapeutic interventions, including the generation of human monoclonal antibodies (hmAbs). hmAbs may be used therapeutically without the drawbacks of chimeric or animal Abs. Several different methods have been used to generate SARS-CoV specific neutralizing hmAbs including the immunization of transgenic mice, cloning of small chain variable regions from naïve and convalescent patients, and the immortalization of convalescent B cells. Irrespective of the techniques used, the majority of hmAbs specifically reacted with the receptor binding domain (RBD) of the spike (S) protein and likely prevented receptor binding. However, several hmAbs that can bind to epitopes either within the RBD, located N terminal of the RBD or in the S2 domain, and neutralize the virus with or without inhibiting receptor binding have been identified. Therapeutic utility of hmAbs has been further elucidated through the identification of potential combinations of hmAbs that could neutralize viral variants including escape mutants selected using hmAbs. These results suggest that a cocktail of hmAbs that can bind to unique epitopes and have different mechanisms of action might be of clinical utility against SARS-CoV infection, and indicate that a similar approach may be applied to treat other viral infections.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / isolation & purification
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / isolation & purification
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology*
  • Epitopes / immunology
  • Humans
  • Immunotherapy / methods*
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Transgenic
  • Protein Binding
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / therapy*
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins / antagonists & inhibitors
  • Viral Envelope Proteins / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antiviral Agents
  • Epitopes
  • Membrane Glycoproteins
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV
  • spike protein, mouse hepatitis virus