Respiratory Syncytial Virus (RSV): Targeting the G Protein Provides a New Approach for an Old Problem.
File(s)
Author(s)
Tripp, Ralph A
Power, Ultan F
Openshaw, Peter JM
Kauvar, Lawrence M
Type
Journal Article
Abstract
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) annually affecting >2 million children in the US <5 years old. In the elderly (>65 years old), RSV results in ∼175,000 hospitalizations annually in the US with worldwide incidence ∼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 pre-term 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 re-emerged 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.
Date Issued
2017-11-08
Date Acceptance
2017-11-08
Citation
Journal of Virology, 2017, 92 (3)
ISSN
1098-5514
Publisher
American Society for Microbiology
Journal / Book Title
Journal of Virology
Volume
92
Issue
3
Copyright Statement
Copyright © 2018 American Society for Microbiology. ripp RA, Power UF, Openshaw PJM, Kauvar LM. 2018. Respiratory syncytial virus: targeting the G protein provides a new approach for an old problem. J Virol 92:e01302-17. https://doi.org/10.1128/JVI.01302-17.
Identifier
PII: JVI.01302-17
Subjects
06 Biological Sciences
07 Agricultural And Veterinary Sciences
11 Medical And Health Sciences
Virology
Publication Status
Published
Article Number
e01302-17