Structural Basis of Respiratory Syncytial Virus Neutralization by Motavizumab

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2010 Jan 26

PMID 20098425

Citations 108

Authors

Jason S McLellan

Man Chen

Albert Kim

Yongping Yang

Barney S Graham

Peter D Kwong

Affiliations

Soon will be listed here.

Abstract

Motavizumab is approximately 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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References

Tao Y, Strelkov S, Mesyanzhinov V, Rossmann M . Structure of bacteriophage T4 fibritin: a segmented coiled coil and the role of the C-terminal domain. Structure. 1997; 5(6):789-98. DOI: 10.1016/s0969-2126(97)00233-5. View

Groothuis J, Simoes E, Hemming V . Respiratory syncytial virus (RSV) infection in preterm infants and the protective effects of RSV immune globulin (RSVIG). Respiratory Syncytial Virus Immune Globulin Study Group. Pediatrics. 1995; 95(4):463-7. View

Johnson S, Oliver C, Prince G, Hemming V, Pfarr D, Wang S . Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J Infect Dis. 1997; 176(5):1215-24. DOI: 10.1086/514115. View

Wu H, Pfarr D, Johnson S, Brewah Y, Woods R, Patel N . Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J Mol Biol. 2007; 368(3):652-65. DOI: 10.1016/j.jmb.2007.02.024. View

Lopez J, Andreu D, CARRENO C, Whyte P, Taylor G, Melero J . Conformational constraints of conserved neutralizing epitopes from a major antigenic area of human respiratory syncytial virus fusion glycoprotein. J Gen Virol. 1993; 74 ( Pt 12):2567-77. DOI: 10.1099/0022-1317-74-12-2567. View

Yin H, Wen X, Paterson R, Lamb R, Jardetzky T . Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation. Nature. 2006; 439(7072):38-44. PMC: 7095149. DOI: 10.1038/nature04322. View

Krissinel E, Henrick K . Inference of macromolecular assemblies from crystalline state. J Mol Biol. 2007; 372(3):774-97. DOI: 10.1016/j.jmb.2007.05.022. View

Liu J, Bartesaghi A, Borgnia M, Sapiro G, Subramaniam S . Molecular architecture of native HIV-1 gp120 trimers. Nature. 2008; 455(7209):109-13. PMC: 2610422. DOI: 10.1038/nature07159. View

Lawrence M, Colman P . Shape complementarity at protein/protein interfaces. J Mol Biol. 1993; 234(4):946-50. DOI: 10.1006/jmbi.1993.1648. View

10.

Smith B, Lawrence M, Colman P . Modelling the structure of the fusion protein from human respiratory syncytial virus. Protein Eng. 2002; 15(5):365-71. DOI: 10.1093/protein/15.5.365. View

11.

. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group. Pediatrics. 1998; 102(3 Pt 1):531-7. View

12.

Arbiza J, Taylor G, Lopez J, Furze J, Wyld S, Whyte P . Characterization of two antigenic sites recognized by neutralizing monoclonal antibodies directed against the fusion glycoprotein of human respiratory syncytial virus. J Gen Virol. 1992; 73 ( Pt 9):2225-34. DOI: 10.1099/0022-1317-73-9-2225. View

13.

Lok S, Kostyuchenko V, Nybakken G, Holdaway H, Battisti A, Sukupolvi-Petty S . Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins. Nat Struct Mol Biol. 2008; 15(3):312-7. DOI: 10.1038/nsmb.1382. View

14.

Beeler J, Van Wyke Coelingh K . Neutralization epitopes of the F glycoprotein of respiratory syncytial virus: effect of mutation upon fusion function. J Virol. 1989; 63(7):2941-50. PMC: 250848. DOI: 10.1128/JVI.63.7.2941-2950.1989. View

15.

Zhao X, Chen F, Megaw A, Sullender W . Variable resistance to palivizumab in cotton rats by respiratory syncytial virus mutants. J Infect Dis. 2004; 190(11):1941-6. DOI: 10.1086/425515. View

16.

Wu H, Pfarr D, Tang Y, An L, Patel N, Watkins J . Ultra-potent antibodies against respiratory syncytial virus: effects of binding kinetics and binding valence on viral neutralization. J Mol Biol. 2005; 350(1):126-44. DOI: 10.1016/j.jmb.2005.04.049. View