期刊
JOURNAL OF VIROLOGY
卷 92, 期 3, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01302-17
关键词
F protein; G protein; RSV; respiratory syncytial virus; monoclonal antibodies; palivizumab
类别
资金
- Wellcome Trust [108818/Z/15/A]
- UK Biotechnology and Biological Sciences Research Council [BB/P004040/1]
- Public Health Service HSC R&D Division, Northern Ireland [COM/5237/15]
- National Institute for Health Research (NIHR)
- NIAID [1R44AI122360-02]
- BBSRC [BB/P004040/1] Funding Source: UKRI
- MRC [MR/R005982/1] Funding Source: UKRI
- Wellcome Trust [108818/Z/15/A] Funding Source: Wellcome Trust
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 similar to 175,000 hospitalizations annually in the United States with a worldwide incidence of similar to 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.
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