Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein

Details

• Alternative Title:
  Nat Commun
• Personal Author:
  Tian, Daiyin ; Battles, Michael B. ; Moin, Syed M. ; Chen, Man ; Modjarrad, Kayvon ; Kumar, Azad ; Kanekiyo, Masaru ; Graepel, Kevin W. ; Taher, Noor M. ; Hotard, Anne L. ; Moore, Martin L. ; Zhao, Min ; Zheng, Zi-Zheng ; Xia, Ning-Shao ; McLellan, Jason S. ; Graham, Barney S.
• Description:
  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.
• Subjects:
  Antibodies, Neutralizing Antibodies, Viral Antibody Specificity Antiviral Agents Crystallography, X-Ray HEK293 Cells Humans Palivizumab Protein Binding Respiratory Syncytial Virus, Human Respiratory Syncytial Virus Infections Surface Plasmon Resonance Viral Fusion Proteins

  More +
• Source:
  Nat Commun. 8.
• Pubmed ID:
  29187732
• Pubmed Central ID:
  PMC5707411
• Document Type:
  Journal Article
• Funding:
  P20 GM113132/GM/NIGMS NIH HHS/United States ; P41 GM103485/GM/NIGMS NIH HHS/United States ; T32 AI007519/AI/NIAID NIH HHS/United States
• Volume:
  8
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:e18d364584bfde4844ae01eb6d3573b04f2df91a809d059d261ee12f631abe31
• Download URL:
  https://stacks.cdc.gov/view/cdc/50271/cdc_50271_DS1.pdf
• File Type:
  [PDF - 2.06 MB ]