Prevention and treatment of bronchopneumonia in mice caused by mouse-adapted variant of avian H5N2 influenza A virus using monoclonal antibody against conserved epitope in the HA stem region

The effects of monoclonal antibody (MAb) C179 recognizing a conformational epitope in the middle of the hemagglutinine (HA) stem region were examined in a mouse model in the experiments of prevention and treatment of lethal b ronchopneumonia caused by influenza A virus of H5 subtype. To model the let hal infection, avian nonpathogenic strain A/mallard duck/Pennsylvania/10218 184 (H5N2) was adapted to mice. This resulted in highly pathogenic pneumovi rulent mouse-adapted (MA) variant, which was characterized. Three amino aci d chances were found in the HA1 subunit of HA of MA virus. One of these was located inside the region of the conformational epitope recognized by MAb, C179. However, this substitution was not significant for the recognition o f HA and virus neutralization by MAb C179 in vitro and in vivo. Intraperito neal administration of two different concentrations of MAb C179 one day bef ore or two days after the virus challenge significantly decreased mortality rate. These results suggest that MAb C179 is efficient not only in the pre vention and treatment of H1 and H2 influenza virus bronchopneumonia, as was reported previously, but also of H5-induced bronchopneumonia as well, and demonstrate in vivo the existence of a common neutralizing epitope in the H As of these three subtypes.