title: Evaluation of the protective efficacy of reshaped human monoclonal antibody RSHZ19 against respiratory syncytial virus in cotton rats.
abstract: Reshaped human MAb RSHZ19, which is specific for the surface fusion protein of respiratory syncytial virus (RSV) is in clinical development for the prevention and treatment of RSV-induced disease in human infants. The current studies profile lung virus clearance and evaluate lung histopathology in MAb-treated, RSV-infected cotton rats, a well characterized model of RSV infection. The highest dose of this MAb (10 mg/kg) administered parenterally 24 h before infection decreased subgroup A or B RSV lung titers to below detectable levels (> or = 2.3 log10 reduction), and significantly reduced lung virus titers (> or = 2.0 log10 reduction) when administered 96 h postinfection. Prophylactic administration of 10 mg/kg RSHZ19 was significantly more protective than 1000 mg/kg conventional human immune serum globulin (HSIg), and protective serum-neutralizing titers in MAb-treated animals (1:32, which correlated with approximately 40 micrograms/ml determined by anti-idiotype ELISA) were significantly lower than those reported previously for HSIg or for convalescent human serum (1:200-1:400). MAb concentration in lung lavages was determined by ELISA to be approximately 1% of the serum MAb concentration, but was not detectable by neutralization assay. The degree of lung histopathology in MAb-treated cotton rats was proportional to lung virus titer, and inversely proportional to the RSHZ19 dose administered. There was no evidence of exacerbated disease in the lungs of MAb-treated animals. These studies thus support the potential clinical utility of RSHZ19 MAb in the prevention and treatment of RSV-induced disease in humans.
authors.affiliation: Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Wyde
authors.forename: D K
authors.initials: DK
authors.lastname: Moore
authors.forename: T
authors.initials: T
authors.lastname: Hepburn
authors.forename: C L
authors.initials: CL
authors.lastname: Silverman
authors.forename: T G
authors.initials: TG
authors.lastname: Porter
authors.forename: M
authors.initials: M
authors.lastname: Gross
authors.forename: G
authors.initials: G
authors.lastname: Taylor
authors.forename: S G
authors.initials: SG
authors.lastname: Demuth
authors.forename: S B
authors.initials: SB
authors.lastname: Dillon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D006801:Humans; D007116:Immunization, Passive; D066298:In Vitro Techniques; D007223:Infant; D008168:Lung / Q000473:pathology; D009500:Neutralization Tests; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D016205:Sigmodontinae; D014760:Viral Fusion Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; C101293:RSHZ19 monoclonal antibody; D014760:Viral Fusion Proteins