James Crowe
Faculty Member
Last active: 3/31/2019

Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein.

Bates JT, Keefer CJ, Slaughter JC, Kulp DW, Schief WR, Crowe JE
Virology. 2014 454-455: 139-44

PMID: 24725940 · PMCID: PMC4004766 · DOI:10.1016/j.virol.2014.02.010

The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (Kon) for binding to RSV F protein, while alteration of dissociation rate (Koff) did not significantly affect neutralizing activity. Interestingly, linkage of reduced Kon with reduced potency mirrored the effect of increased Kon found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants.

Copyright © 2014 Elsevier Inc. All rights reserved.

MeSH Terms (11)

Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Antibodies, Neutralizing Drug Resistance, Viral Humans Kinetics Mutation Palivizumab Protein Binding Respiratory Syncytial Viruses Viral Fusion Proteins

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