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J Virol. 2018 Jan 17;92(3). pii: e01302-17. doi: 10.1128/JVI.01302-17. Print 2018 Feb 1.

Respiratory Syncytial Virus: Targeting the G Protein Provides a New Approach for an Old Problem.

Author information

1
University of Georgia, College of Veterinary Medicine, Department of Infectious Diseases, Athens, Georgia, USA.
2
Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
3
Imperial College London, London, United Kingdom.
4
Trellis Bioscience, Menlo Park, California, USA lkauvar@trellisbio.com.

Abstract

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) annually affecting >2 million children in the United States <5 years old. In the elderly (>65 years old), RSV results in ∼175,000 hospitalizations annually in the United States with a worldwide incidence of ∼34 million. There is no approved RSV vaccine, and treatments are limited. Recently, a phase 3 trial in the elderly using a recombinant RSV F protein vaccine failed to meet its efficacy objectives, namely, prevention of moderate-to-severe RSV-associated LRTI and reduced incidence of acute respiratory disease. Moreover, a recent phase 3 trial evaluating suptavumab (REGN2222), an antibody to RSV F protein, did not meet its primary endpoint of preventing medically attended RSV infections in preterm infants. Despite these setbacks, numerous efforts targeting the RSV F protein with vaccines, antibodies, and small molecules continue based on the commercial success of a monoclonal antibody (MAb) against the RSV F protein (palivizumab). As the understanding of RSV biology has improved, the other major coat protein, the RSV G protein, has reemerged as an alternative target reflecting progress in understanding its roles in infecting bronchial epithelial cells and in altering the host immune response. In mouse models, a high-affinity, strain-independent human MAb to the RSV G protein has shown potent direct antiviral activity combined with the alleviation of virus-induced immune system effects that contribute to disease pathology. This MAb, being prepared for clinical trials, provides a qualitatively new approach to managing RSV for populations not eligible for prophylaxis with palivizumab.

KEYWORDS:

F protein; G protein; RSV; monoclonal antibodies; palivizumab; respiratory syncytial virus

PMID:
29118126
PMCID:
PMC5774885
DOI:
10.1128/JVI.01302-17
[Indexed for MEDLINE]
Free PMC Article

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