Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein
[2];
[3];
[3]
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA; Department of Pulmonology, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China
- Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, 03755, USA
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
- Walter Reed Army Institute of Research, Silver Spring, MD, 20910, USA; Henry M. Jackson Foundation, Bethesda, MD, 20817, USA
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37208, USA
- Department of Pediatrics, Emory University, Atlanta, GA, 30322, USA; Division of Select Agents and Toxins, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA
- Department of Pediatrics, Emory University, Atlanta, GA, 30322, USA; Meissa Vaccines, Inc South, San Francisco, CA, 94080, USA
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, 361005, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science Xiamen University, Xiamen, Fujian, 361005, China
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, 361005, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, Fujian, 361005, China
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, 361005, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences Xiamen University, Xiamen, Fujian, 361005, China
A licensed vaccine for respiratory syncytial virus (RSV) is unavailable, and passive prophylaxis with the antibody palivizumab is restricted to high-risk infants. Recently isolated antibodies 5C4 and D25 are substantially more potent than palivizumab, and a derivative of D25 is in clinical trials. Here we show that unlike D25, 5C4 preferentially neutralizes subtype A viruses. The crystal structure of 5C4 bound to the RSV fusion (F) protein reveals that the overall binding mode of 5C4 is similar to that of D25, but their angles of approach are substantially different. Mutagenesis and virological studies demonstrate that RSV F residue 201 is largely responsible for the subtype specificity of 5C4. These results improve our understanding of subtype-specific immunity and the neutralization breadth requirements of next-generation antibodies, and thereby contribute to the design of broadly protective RSV vaccines.
- Research Organization:
- Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Science Foundation (NSF); National Natural Science Foundation of China (NSFC); National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID)
- Grant/Contract Number:
- AC02-98CH10886; DMR-1332208; GM-103485; 81361120408; 81401668; 5T32AI007519 P20GM113132
- OSTI ID:
- 1624058
- Journal Information:
- Nature Communications, Vol. 8, Issue 1; ISSN 2041-1723
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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