Monoclonal Antibody Therapy Protects Pharmacologically Immunosuppressed Mice from Lethal Infection with Influenza B...

Human influenza A and B viruses are highly contagious and cause similar illnesses and seasonal epidemics. Currently available antiviral drugs have limited efficacy in humans with compromised immune systems; therefore, alternative strategies for protection are needed. Here, we investigated whether monoclonal antibodies (MAbs) targeting hemagglutinin (HA) and/or neuraminidase (NA) proteins would protect immunosuppressed mice from severe infections with influenza B virus. Pharmacologically immunosuppressed BALB/c mice were inoculated with B/Brisbane/60/2008 (BR/08) influenza virus and were treated with a single dose of 1, 5, or 25 mg/kg of body weight per day of either an anti-HA MAb (1D2) or an anti-NA MAb (1F2) starting at 24 hours postinoculation (hpi). Monotherapy with 1D2 or 1F2 MAbs provided dose-dependent protection of mice, with decreased BR/08 virus replication and spread in the mouse lungs, compared with those of controls. Combination treatment with 1D2 and 1F2 provided greater protection than did monotherapy, even when started at 48 hpi. Virus spread was also efficiently restrained within the lungs, being limited to 6%, 10%, and 10% of that seen in active infection when treatment was initiated at 24, 48, and 72 hpi, respectively. In most cases, the expression of cytokines and chemokines was altered according to when treatment was initiated. Higher expression of proinflammatory IP-10 and MCP-1 in combination-treatment groups, but not in monotherapy groups, to some extent, promoted better control of virus spread within the lungs. This study demonstrates the potential value of MAb immunotherapy in treating influenza in immunocompromised hosts who are at increased risk of severe disease.