The prophylactic administration of a monoclonal antibody against human metapneumovirus attenuates viral disease and airways hyperresponsiveness in mice.
BACKGROUND
Human metapneumovirus (hMPV) is one of the most frequent causes of respiratory tract infections in children. Our objective was to assess the prophylactic benefit of a monoclonal antibody (mAb) against the hMPV fusion protein in a murine model.


METHODS
BALB/c mice received one intramuscular injection of either 5 or 10 mg/kg of mAb 338 (MedImmune, Inc.) and were infected intranasally 24 h later with 1x10(8) TCID50 (50% tissue culture infectious dose) of hMPV. On days 5 and 42 post-infection, lung samples were collected for determination of viral titres and for histopathological studies. Pulmonary function was characterized by plethysmography.


RESULTS
Mean lung viral titres were significantly lower in mice treated with 5 or 10 mg/kg of mAb 338 compared with infected controls on day 5 (283, 45.6 and 1.49x10(5) TCID50/g, respectively; P<0.05). Similarly, lung viral RNA copies were significantly reduced in treated mice on day 42 (292, 101 and 607 copies per 0.01 g of lungs for mice that received 5 mg/kg, 10 mg/kg or no mAb, respectively; P<0.05). Histopathological changes characterized by important alveolar and interstitial inflammation were less severe in treated mice on days 5 and 42 compared with control. Airways obstruction was also significantly reduced in both treated groups on days 5 and 42, but development of hyperresponsiveness following the acute phase of infection was only significantly reduced in 10 mg/kg treated mice.


CONCLUSIONS
Prophylactic administration of mAb 338 attenuates acute and late consequences of hMPV disease in this mouse model.
Hamelin
Marie-Eve
ME
Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Québec, Laval University, Québec City, Québec, Canada.
Couture
Christian
C
Sackett
Melanie
M
Kiener
Peter
P
Suzich
JoAnn
J
Ulbrandt
Nancy
N
Boivin
Guy
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control* / Q000821:virology; D004305:Dose-Response Relationship, Drug; D029121:Metapneumovirus / Q000276:immunology*; D051379:Mice; D018184:Paramyxoviridae Infections / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*
D000911:Antibodies, Monoclonal