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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.
- Source :
-
Virology [Virology] 2014 Apr; Vol. 454-455, pp. 139-44. Date of Electronic Publication: 2014 Mar 03. - Publication Year :
- 2014
-
Abstract
- 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.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Antibodies, Monoclonal metabolism
Antibodies, Monoclonal, Humanized metabolism
Antibodies, Neutralizing metabolism
Drug Resistance, Viral
Humans
Kinetics
Mutation
Palivizumab
Protein Binding
Viral Fusion Proteins metabolism
Antibodies, Monoclonal immunology
Antibodies, Monoclonal, Humanized immunology
Antibodies, Neutralizing immunology
Respiratory Syncytial Viruses genetics
Respiratory Syncytial Viruses immunology
Viral Fusion Proteins genetics
Viral Fusion Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0341
- Volume :
- 454-455
- Database :
- MEDLINE
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 24725940
- Full Text :
- https://doi.org/10.1016/j.virol.2014.02.010