title: Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus.
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.
authors.affiliation: MedImmune Inc., Gaithersburg, Maryland 20878, USA.
authors.forename: S
authors.initials: S
authors.lastname: Johnson
authors.forename: C
authors.initials: C
authors.lastname: Oliver
authors.forename: G A
authors.initials: GA
authors.lastname: Prince
authors.forename: V G
authors.initials: VG
authors.lastname: Hemming
authors.forename: D S
authors.initials: DS
authors.lastname: Pfarr
authors.forename: S C
authors.initials: SC
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Dormitzer
authors.forename: J
authors.initials: J
authors.lastname: O'Grady
authors.forename: S
authors.initials: S
authors.lastname: Koenig
authors.forename: J K
authors.initials: JK
authors.lastname: Tamura
authors.forename: R
authors.initials: R
authors.lastname: Woods
authors.forename: G
authors.initials: G
authors.lastname: Bansal
authors.forename: D
authors.initials: D
authors.lastname: Couchenour
authors.forename: E
authors.initials: E
authors.lastname: Tsao
authors.forename: W C
authors.initials: WC
authors.lastname: Hall
authors.forename: J F
authors.initials: JF
authors.lastname: Young
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D015707:HN Protein; D006801:Humans; D008969:Molecular Sequence Data; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D016205:Sigmodontinae; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G