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Development of a Humanized Monoclonal Antibody (MEDI‐493) with Potent In Vitro and In Vivo Activity against Respiratory Syncytial Virus
Open accessAbstract
Neutralizing polyclonal antibody to respiratory syncytial virus (RSV) has been shown to be an effective prophylactic agent when administered intravenously in high-risk infants. This study describes the generation of a humanized monoclonal antibody, MEDI-493, that recognizes a conserved neutralizing epitope on the F glycoprotein of RSV. The affinity of MEDI-493 was found to be equal to or slightly better than an isotype-matched chimeric derivative of the parent antibody. In plaque reduction, microneutralization, and fusion-inhibition assays, MEDI-493 was significantly more potent than the polyclonal preparation. Broad neutralization of a panel of 57 clinical isolates of the RSV A and B subtypes was demonstrated. Pretreatment of cotton rats with MEDI-493 resulted in 99% reduction of lung RSV titers at a dose of 2.5 mg/kg, corresponding to a serum concentration of 25-30 microg/mL. Further, MEDI-493 did not induce increased RSV infection or pathology in either a primary or a secondary challenge.
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KIM, H. W., CANCHOLA, J. G., BRANDT, C. D., PYLES, G., CHANOCK, R. M., JENSEN, K., & PARROTT, R. H. (1969) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a120955 · Cited by 1,981
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Cited by
Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus
McLellan, J. S., Chen, M., Joyce, M. G., Sastry, M., Stewart-Jones, G. B. E., Yang, Y., Zhang, B., Chen, L., Srivatsan, S., Zheng, A., et al. (2013) · Science · doi:10.1126/science.1243283 · Cited by 1,126
Structure of RSV Fusion Glycoprotein Trimer Bound to a Prefusion-Specific Neutralizing Antibody
McLellan, J. S., Chen, M., Leung, S., Graepel, K. W., Du, X., Yang, Y., Zhou, T., Baxa, U., Yasuda, E., Beaumont, T., et al. (2013) · Science · doi:10.1126/science.1234914 · Cited by 883
Virus entry: molecular mechanisms and biomedical applications
Dimitrov, D. S. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro817 · Cited by 701
Traggiai, E., Becker, S., Subbarao, K., Kolesnikova, L., Uematsu, Y., Gismondo, M. R., Murphy, B. R., Rappuoli, R., & Lanzavecchia, A. (2004) · Nature Medicine · doi:10.1038/nm1080 · Cited by 697
A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism
Krarup, A., Truan, D., Furmanova-Hollenstein, P., Bogaert, L., Bouchier, P., Bisschop, I. J. M., Widjojoatmodjo, M. N., Zahn, R., Schuitemaker, H., McLellan, J. S., et al. (2015) · Nature Communications · doi:10.1038/ncomms9143 · Cited by 383
Metadata
- Authors
- Johnson, S., Oliver, C., Prince, G. A., Hemming, V. G., Pfarr, D. S., Wang, S., Dormitzer, M., O'Grady, J., Koenig, S., Tamura, J. K., Woods, R., Bansal, G., Couchenour, D., Tsao, E., Hall, W. C., & Young, J. F.
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-11
- Volume
- 176
- Issue
- 5
- Pages
- 1215-1224
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2019706667
- Cited by
- 641
- References
- 2
- FWCI
- 15.81
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Johnson, S., Oliver, C., Prince, G. A., Hemming, V. G., Pfarr, D. S., Wang, S., Dormitzer, M., O'Grady, J., Koenig, S., Tamura, J. K., Woods, R., Bansal, G., Couchenour, D., Tsao, E., Hall, W. C., & Young, J. F. (1997). Development of a Humanized Monoclonal Antibody (MEDI‐493) with Potent In Vitro and In Vivo Activity against Respiratory Syncytial Virus. The Journal of Infectious Diseases. https://doi.org/10.1086/514115
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
