Brief Communication | Published:

Structural basis of respiratory syncytial virus neutralization by motavizumab

Nature Structural & Molecular Biology volume 17, pages 248250 (2010) | Download Citation

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Accessions

Primary accessions

Protein Data Bank

References

  1. 1.

    World Health Organization. Acute respiratory infection (World Health Organization, Geneva, 2009; accessed 6 January 2010). <>

  2. 2.

    et al. J. Am. Med. Assoc. 289, 179–186 (2003).

  3. 3.

    , & Pediatrics 95, 463–467 (1995).

  4. 4.

    et al. J. Infect. Dis. 176, 1215–1224 (1997).

  5. 5.

    & J. Virol. 63, 2941–2950 (1989).

  6. 6.

    et al. J. Gen. Virol. 73, 2225–2234 (1992).

  7. 7.

    et al. J. Gen. Virol. 74, 2567–2577 (1993).

  8. 8.

    The IMpact-RSV Study Group. Pediatrics 102, 531–537 (1998).

  9. 9.

    et al. J. Mol. Biol. 368, 652–665 (2007).

  10. 10.

    et al. J. Mol. Biol. 350, 126–144 (2005).

  11. 11.

    & USPTO Patent 7229618 (2007).

  12. 12.

    , & Protein Eng. 15, 365–371 (2002).

  13. 13.

    & J. Mol. Biol. 372, 774–797 (2007).

  14. 14.

    & J. Mol. Biol. 234, 946–950 (1993).

  15. 15.

    , , & J. Infect. Dis. 190, 1941–1946 (2004).

  16. 16.

    , , , & USPTO Patent application 11/230,593 (2006).

  17. 17.

    , , , & Nature 439, 38–44 (2006).

  18. 18.

    , , & Structure 5, 789–798 (1997).

  19. 19.

    et al. Nat. Struct. Mol. Biol. 15, 312–317 (2008).

  20. 20.

    , , , & Nature 455, 109–113 (2008).

Download references

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.

Author information

Affiliations

  1. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

    • Jason S McLellan
    • , Man Chen
    • , Albert Kim
    • , Yongping Yang
    • , Barney S Graham
    •  & Peter D Kwong

Authors

  1. Search for Jason S McLellan in:

  2. Search for Man Chen in:

  3. Search for Albert Kim in:

  4. Search for Yongping Yang in:

  5. Search for Barney S Graham in:

  6. Search for Peter D Kwong in:

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Peter D Kwong.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Methods, Supplementary Figues 1–4 and Supplementary Table 1

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nsmb.1723

Further reading