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.

Infection with human metapneumovirus predisposes mice to severe pneumococcal pneumonia.

Human metapneumovirus (hMPV) is a recently described paramyxovirus that causes respiratory tract infections. Prior clinical studies have highlighted the importance of respiratory viruses, such as influenza virus, in facilitating secondary bacterial infections and increasing host immunopathology. The objective of the present work was to evaluate the effects of initial viral infection with hMPV or influenza A virus followed by Streptococcus pneumoniae superinfection 5 days later in a murine model. Both groups of superinfected mice demonstrated significant weight loss (mean of 15%) and higher levels of airway obstruction (mean enhanced pause value of 2.7) compared to those of mice infected with hMPV, influenza virus, or pneumococcus alone. Bacterial counts increased from 5 x 10(2) CFU/lung in mice infected with pneumococcus only to 10(7) and 10(9) CFU/lung in mice with prior infections with hMPV and influenza A virus, respectively. A more pronounced interstitial and alveolar inflammation correlated with higher levels of inflammatory cytokines and chemokines such as interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, IL-12, monocyte chemotactic protein 1, macrophage inflammatory protein 1alpha, KC, and granulocyte colony-stimulating factor, as well as greater expression of Toll-like receptor 2 (TLR2), TLR6, TLR7, and TLR13 in the lungs of superinfected animals compared to results for single infections, with similar immunological effects seen in both coinfection models. Prior infection with either hMPV or influenza A virus predisposes mice to severe pneumococcus infection.