A direct comparison of the activities of two humanized respiratory syncytial virus monoclonal antibodies: MEDI-493 and RSHZl9.
Two humanized monoclonal antibodies, MEDI-493 and RSHZ19, 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, RSHZ19 failed to show significant efficacy. In new studies, the in vitro and in vivo activities of MEDI-493 and RSHZ19 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 RSHZ19 in antigen binding, RSV neutralization, and fusion inhibition assays. Although both MEDI-493 and RSHZ19 were effective against A and B subtypes of RSV in the cotton rat model of RSV infection, 2- to 4-fold higher doses of RSHZ19 were required for similar protection. The enhanced activity of MEDI-493 compared with RSHZ19 may, in part, explain its better clinical effect.
Johnson
S
S
MedImmune, Inc., Gaithersburg, MD 20878, USA. johnsons@medimmune.com
Griego
S D
SD
Pfarr
D S
DS
Doyle
M L
ML
Woods
R
R
Carlin
D
D
Prince
G A
GA
Koenig
S
S
Young
J F
JF
Dillon
S B
SB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000915:Antibody Affinity; D002459:Cell Fusion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015707:HN Protein; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D009500:Neutralization Tests; D000069455:Palivizumab; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D016205:Sigmodontinae; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015707:HN Protein; D007074:Immunoglobulin G; C101293:RSHZ19 monoclonal antibody; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C116204:attachment protein G; D000069455:Palivizumab