A direct comparison of the activities of two humanized respiratory syncytial virus monoclonal antibodies: MEDI-493 and RSHZ19

Two humanized monoclonal antibodies, MEDI-493 and RSHZ19, were developed in dependently as potential improvements over RSV-IGIV for prevention of respi ratory syncytial virus (RSV) infection. RSV-IGIV is a polyclonal human anti body preparation for intravenous infusion enriched for RSV neutralizing act ivity. A phase III clinical trial showed that MEDI-493 significantly reduce d hospitalizations due to RSV infection. In a separate trial, RSHZ19 failed to show significant efficacy. In new studies, the in vitro and in vivo act ivities of MEDI-493 and RSHZ19 were compared to determine whether the diffe rent clinical results are related to differences in biologic activity. MEDI -493 was consistently 4- to 5-fold more potent than RSHZ19 in antigen bindi ng, RSV neutralization, and fusion inhibition assays. Although both MEDI-49 3 and RSHZ19 were effective against A and B subtypes of RSV in the cotton r at model of RSV infection, 2- to 4-fold higher doses of RSHZ19 were require d for similar protection. The enhanced activity of MEDI-493 compared with R SHZ19 may, in part, explain its better clinical effect.