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  2. Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus

Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus

  • J Infect Dis. 1997 Nov;176(5):1215-24. doi: 10.1086/514115.
S Johnson 1 C Oliver G A Prince V G Hemming D S Pfarr S C Wang M Dormitzer J O'Grady S Koenig J K Tamura R Woods G Bansal D Couchenour E Tsao W C Hall J F Young
Affiliations

Affiliation

  • 1 MedImmune Inc., Gaithersburg, Maryland 20878, USA.
PMID: 9359721 DOI: 10.1086/514115
Abstract

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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