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Published on: January 26, 2019
Clinical Potential of Prefusion RSV F-specific Antibodies
Iebe Rossey1, Jason S McLellan2, Xavier Saelens1
1VIB-UGent Center for Medical Biotechnology, Technologiepark 927, Ghent, B-9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, B-9052, Belgium.
Insights
Respiratory Syncytial Virus (RSV) fusion protein (F) antibodies can prevent infection. Targeting the prefusion form of the F protein offers greater potential for clinical applications against RSV.
Area of Science:
- Virology and Immunology
- Vaccine Development
Background:
- Human Respiratory Syncytial Virus (RSV) is a major cause of lower respiratory tract infections in infants.
- The RSV fusion (F) protein is critical for viral entry, mediating membrane fusion and undergoing conformational changes from prefusion to postfusion states.
- Antibodies targeting the F protein can neutralize RSV and prevent infection.
Purpose of the Study:
- To explain how F-specific antibodies protect against RSV.
- To highlight the clinical potential of targeting the prefusion conformation of the RSV F protein.
Main Methods:
- Review and analysis of existing literature on RSV F protein structure and antibody interactions.
- Comparison of the neutralizing activity of antibodies targeting different F protein conformations.
Main Results:
- Antibodies targeting the RSV F protein are effective in preventing viral entry and reducing disease.
- Prefusion F-specific antibodies generally exhibit stronger RSV-neutralizing activity than antibodies that bind the postfusion conformation.
Conclusions:
- Targeting the prefusion conformation of the RSV F protein is a promising strategy for developing effective RSV therapeutics and vaccines.
- Understanding the structural dynamics of the F protein is crucial for designing antibodies with enhanced neutralizing capabilities.
Abstract:
Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in the very young. The RSV fusion protein (F) is essential for virus entry because it mediates viral and host membrane fusion. During this fusion process F is converted from a metastable prefusion conformation into an energetically favored postfusion state. Antibodies that target F can prevent viral entry and reduce disease caused by RSV. During recent years, many prefusion F-specific antibodies have been described. These antibodies typically have stronger RSV-neutralizing activity compared to those that also bind F in the postfusion conformation. Here, we describe how F-specific antibodies protect against RSV and why specifically targeting prefusion F could have great clinical potential.
