Prophylactic and therapeutic benefits of a monoclonal antibody against the fusion protein of human metapneumovirus in a mouse model.
Human metapneumovirus (HMPV) is a paramyxovirus causing acute respiratory tract infections in humans. The effects of a monoclonal antibody (MAb 338, MedImmune, Inc.) directed against the HMPV fusion protein were assessed in vivo. Different groups of BALB/c mice received an intraperitoneal injection of 25 or 50mg/kg of MAb 338 either 24h before or 48h after viral infection. Lung samples were collected on days 5 and 42 after infection for determination of viral titers and histopathological changes. Pulmonary functions were also evaluated by plethysmography. On day 5 post-infection, lung viral titers were significantly decreased in mice treated with 25 or 50mg/kg before or after viral infection compared to HMPV-infected control mice. Similarly, HMPV copy numbers on day 42 were decreased for all prophylactic and therapeutic interventions. Histopathological changes were also less severe in all treated groups of mice on days 5 and 42 post-infection, correlating with decreased airways obstruction. Finally, on day 42, all treated groups had a significant decrease in airways hyperresponsiveness following treatment with MAb 338. Both prophylactic and, to a lesser extent, therapeutic administration of MAb 338 improved acute and late consequences of HMPV infection in a relevant mouse model.
Hamelin
Marie-Eve
ME
Research Center in Infectious Diseases of the Centre Hospitalier Universitaire de Québec and Laval University, 2705 Laurier blvd, Québec City, QC, Canada G1V 4G2.
Gagnon
Constance
C
Prince
Gregory A
GA
Kiener
Peter
P
Suzich
Joann
J
Ulbrandt
Nancy
N
Boivin
Guy
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000276:immunology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000276:immunology / Q000627:therapeutic use; D004195:Disease Models, Animal; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008173:Lung Diseases, Obstructive / Q000188:drug therapy / Q000473:pathology; D029121:Metapneumovirus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018184:Paramyxoviridae Infections / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology; D016133:Polymerase Chain Reaction; D012130:Respiratory Hypersensitivity; D012137:Respiratory System; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D014760:Viral Fusion Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000998:Antiviral Agents; D014760:Viral Fusion Proteins