A Direct Comparison of the Activities of Two Humanized Respiratory Syncytial Virus Monoclonal Antibodies: MEDI‐493 and RSHZl9

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Abstract
Two humanized monoclonal antibodies, MEDI-493 and RSHZl9, were developed independently as potential improvements over RSV-IGIV for prevention of respiratory syncytial virus (RSV) infection. RSV-IGIV is a polyclonal human antibody preparation for intravenous infusion enriched for RSV neutralizing activity. A phase III clinical trial showed that MEDI-493 significantly reduced hospitalizations due to RSV infection. In a separate trial, RSHZl9 failed to show significant efficacy. In new studies, the in vitro and in vivo activities of MEDI-493 and RSHZl9 were compared to determine whether the different clinical results are related to differences in biologic activity. MEDI-493 was consistently 4- to 5-fold more potent than RSHZl9 in antigen binding, RSV neutralization, and fusion inhibition assays. Although both MEDI-493 and RSHZl9 were effective against A and B subtypes of RSV in the cotton rat model of RSV infection, 2- to 4-fold higher doses of RSHZl9 were required for similar protection. The enhanced activity of MEDI-493 compared with RSHZl9 may, in part, explain its better clinical effect.