Protection Against Influenza B Viruses by Human Monoclonal Antibodies that Target the Neuraminidase Active Site

Influenza B virus infections can cause severe disease in pediatric patients and in the elderly. The risk of such disease is exacerbated by the lower clinical effectiveness of some antiviral drugs against influenza B compared with influenza A virus infections especially in children. Recent efforts have advanced neuraminidase (NA) as a reemerging candidate for novel broadly protective influenza virus vaccines. Such efforts are assisted by the identification of new broadly neutralizing and protective antibodies that target the NA active site. Here, we describe seven human anti-NA monoclonal antibodies (mAbs) isolated from an influenza B virus-infected patient. All antibodies block NA activity, neutralize virus, mediate effector functions and are broadly protective in vivo. We show that the two most potent mAbs inhibit NA activity by blocking the active site using long CDR-H3 loops that engage highly conserved residues amongst influenza B viruses. The comprehensive functional and structural characterization of these antibodies provides a blueprint for the development of improved vaccines and therapeutics against influenza B viruses.