Comparative effects of two neutralizing anti-respiratory syncytial virus (RSV) monoclonal antibodies in the RSV murine model: time versus potency.
Respiratory syncytial virus (RSV) is the leading viral pathogen responsible for bronchiolitis and pneumonia in infants and young children worldwide. We have previously shown in the mouse model that treatment with an anti-RSV neutralizing monoclonal antibody (MAb) against the F glycoprotein of RSV, palivizumab, decreased lung inflammation, airway obstruction, and postmethacholine airway hyperresponsiveness. MEDI-524, or Numax, is a new MAb derived from palivizumab with enhanced neutralizing activity against RSV. We compared the effects of these two MAbs on different markers of disease severity using the murine model of RSV infection. BALB/c mice were intranasally inoculated with RSV A2. Palivizumab or MEDI-524 was administered once at either 24 h before or 48 h after RSV inoculation. Regardless of the time of administration, all treated mice showed significantly decreased RSV loads in bronchoalveolar lavage samples measured by plaque assay. Only MEDI-524 given at -24 h significantly decreased lung RSV RNA loads on days 5 and 28 after RSV inoculation. Pulmonary histopathologic scores, airway obstruction, and postmethacholine airway hyperresponsiveness were significantly reduced in mice treated with MEDI-524 at 24 h before inoculation, compared with untreated controls and the other regimens evaluated. MEDI-524 was superior to palivizumab on several outcome variables of RSV disease assessed in the mouse model: viral replication, inflammatory and clinical markers of acute disease severity, and long-term pulmonary abnormalities.
Mejías
Asunción
A
Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-906, USA.
Chávez-Bueno
Susana
S
Ríos
Ana María
AM
Aten
Mónica Fonseca
MF
Raynor
Brett
B
Peromingo
Estrella
E
Soni
Perla
P
Olsen
Kurt D
KD
Kiener
Peter A
PA
Gómez
Ana María
AM
Jafri
Hasan S
HS
Ramilo
Octavio
O
D000402:Airway Obstruction / Q000517:prevention & control; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D000069455:Palivizumab; D016133:Polymerase Chain Reaction; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents; C506968:motavizumab; D000069455:Palivizumab