Combination therapy using monoclonal antibodies against respiratory syncytial virus (RSV) G glycoprotein protects from RSV disease in BALB/c mice

PLoS One. 2012;7(12):e51485. doi: 10.1371/journal.pone.0051485. Epub 2012 Dec 27.

Abstract

Therapeutic options to control respiratory syncytial virus (RSV) are limited, thus development of new therapeutics is high priority. Previous studies with a monoclonal antibody (mAb) reactive to an epitope proximal to the central conserved region (CCR) of RSV G protein (mAb 131-2G) showed therapeutic efficacy for reducing pulmonary inflammation RSV infection in BALB/c mice. Here, we show a protective effect in RSV-infected mice therapeutically treated with a mAb (130-6D) reactive to an epitope within the CCR of G protein, while treatment with a mAb specific for a carboxyl G protein epitope had no effect. Combined treatment with mAbs 130-6D and 131-2G significantly decreased RSV-associated pulmonary inflammation compared to either antibody alone. The results suggest that anti-RSV G protein mAbs that react at or near the CCR and can block RSV G protein-mediated activities are effective at preventing RSV disease and may be an effective strategy for RSV therapeutic treatment.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Viral / immunology*
  • Chemotaxis
  • Drug Therapy, Combination
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology
  • Female
  • Flow Cytometry
  • Humans
  • Immunization
  • Immunoenzyme Techniques
  • Lymphocytes / immunology
  • Lymphocytes / pathology
  • Lymphocytes / virology
  • Mice
  • Mice, Inbred BALB C
  • Pneumonia / diagnosis
  • Pneumonia / immunology
  • Pneumonia / prevention & control*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Respiratory Syncytial Virus Infections / complications
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Viruses / genetics
  • Respiratory Syncytial Viruses / immunology*
  • Respiratory Syncytial Viruses / isolation & purification
  • Reverse Transcriptase Polymerase Chain Reaction
  • Viral Fusion Proteins / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Epitopes
  • G glycoprotein, Respiratory syncytial virus
  • RNA, Messenger
  • Viral Fusion Proteins