Evaluation of the protective efficacy of reshaped human monoclonal antibody RSHZ19 against respiratory syncytial virus in cotton rats.
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.
Wyde
P R
PR
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Moore
D K
DK
Hepburn
T
T
Silverman
C L
CL
Porter
T G
TG
Gross
M
M
Taylor
G
G
Demuth
S G
SG
Dillon
S B
SB
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; C101293:RSHZ19 monoclonal antibody; D014760:Viral Fusion Proteins