THE PHARMACOKINETICS, ANTIGENICITY, AND FUSION-INHIBITION ACTIVITY OFRSHZ19, A HUMANIZED MONOCLONAL-ANTIBODY TO RESPIRATORY SYNCYTIAL VIRUS, IN HEALTHY-VOLUNTEERS

Single ascending doses of RSHZ19 (also known as SB 209763), a humanize d monoclonal antibody (MAb) directed to the fusion protein of respirat ory syncytial virus, were administered to healthy men to evaluate the safety, pharmacokinetics, antigenicity, and fusion inhibition (FI) act ivity of RSHZ19, Doses of RSHZ19 (0.025-10.0 mg/kg) or placebo were in fused over 30 min, and subjects were followed for 10 weeks. Plasma con centrations of RSHZ19 and RSHZ19-specific antibodies were determined b y ELISAs. FI titers were used to evaluate the ability of plasma to inh ibit virus-induced fusion of VERO cells previously infected with RS Lo ng strain virus, Twenty-six subjects, mean age 24, completed the study , RSHZ19 was safe and well tolerated, and no subject developed antibod ies to RSHZ19 during follow-up, RSHZ19 had low plasma clearance and a half-life of similar to 23 days, similar to native IgG. Increases in F I titers relative to pretreatment levels were seen 24 h after MAb admi nistration in all 4 subjects given 10 mg/kg and in 2 of 4 given 5 mg/k g.