Broadly-neutralizing antibodies that bind to the influenza hemagglutinin stalk domain enhance the effectiveness of neuraminidase inhibitors via Fc-mediated effector functions

Summary The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next generation universal influenza vaccines. Protection provided by hemagglutinin stalk binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level, and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individual’s titers of stalk-binding antibodies, and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.