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Structural basis of respiratory syncytial virus neutralization by motavizumab

Abstract

Motavizumab is tenfold more potent than its predecessor, palivizumab (Synagis), the FDA-approved monoclonal antibody used to prevent respiratory syncytial virus (RSV) infection. The structure of motavizumab in complex with a 24-residue peptide corresponding to its epitope on the RSV fusion (F) glycoprotein reveals the structural basis for this greater potency. Modeling suggests that motavizumab recognizes a different quaternary configuration of the F glycoprotein than that observed in a homologous structure.

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Figure 1: Structural basis of motavizumab binding to its F glycoprotein epitope.
Figure 2: Motavizumab binding to RSV F glycoprotein.

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Acknowledgements

The authors would like to thank L. Shapiro and members of the Structural Biology Section, Vaccine Research Center, for helpful comments, and J. Gonczy and the staff at SER-CAT (Southeast Regional Collaborative Access Team) for help with X-ray diffraction data collection. Support for this work was provided by the Intramural Research Program (US National Institute of Allergy and Infectious Diseases). Use of insertion device 22 (SER-CAT) at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract W-31-109-Eng-38.

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Authors and Affiliations

Authors

Contributions

J.S.M., B.S.G. and P.D.K. designed experiments and analyzed data; J.S.M. also prepared, crystallized and solved the structure of the motavizumab–peptide complex and performed the biochemical and biophysical experiments; M.C. performed the neutralization experiments; Y.Y. and A.K. expressed and purified the RSV F0 Fd glycoprotein and motavizumab IgG, respectively.

Corresponding author

Correspondence to Peter D Kwong.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Figues 1–4 and Supplementary Table 1 (PDF 912 kb)

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McLellan, J., Chen, M., Kim, A. et al. Structural basis of respiratory syncytial virus neutralization by motavizumab. Nat Struct Mol Biol 17, 248–250 (2010). https://doi.org/10.1038/nsmb.1723

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