Designed, broadly protective antibodies directed against influenza B.

Influenza B viruses (IBVs) cause a quarter of all human influenza cases and in some seasons even dominate influenza A. In the past 3 decades, the world has witnessed a worrying antigenic diversification of IBVs, first with the emergence in the 1980s of the steadily separating Victoria and Yamagata antigenic lineages. More recently, the Yamagata lineage in its turn has started to bifurcate antigenically. In general, currently licensed antivirals work less efficiently against IBV compared with influenza A viruses. Therefore, there is an urgent need to develop drugs that can potently and broadly restrict IBVs. In this project, we will isolate single domain antibodies that can neutralize a broad range of IBVs, by binding to conserved sites on the surface of the viral hemagglutinin and neuraminidase. These single domain antibodies will first be evaluated in vitro for their anti-influenza B potency and broadness. The best performing hemagglutinin- and neuraminidase-specific single domain antibodies will be combined in one format by making genetic fusions with a conventional IgG Fc domain. Finally, the resulting recombinant molecules will be formulated for their delivery as inhaled biopharmaceuticals, and tested in vivo for their protective potential and broadness against IBV challenge infection.