Human neutralizing antibodies targeting the measles virus hemagglutinin and fusion surface proteins

Measles virus (MeV), a highly transmissible paramyxovirus, can cause severe complications and death, particularly in infants and young children. How and where human antibodies target and neutralize MeV remain unclear. Here, we report a panel of human monoclonal antibodies (mAbs) specific for MeV hemagglutinin (H) and fusion (F) surface proteins, derived from the memory B cells of a Measles-Mumps-Rubella (MMR) vaccinee. We mapped four and five major epitope clusters on H and F, respectively, and structurally characterized representative mAbs from each epitope cluster. MAbs against both H and F offer broad, potent, picomolar-level neutralization and substantially reduce viral loads in vivo when delivered before or after viral exposure. High-resolution cryo-electron microscopy of mAb complexes with H and F reveal highly conserved contact sites of the most protective antibodies. Characterization of these fully human mAbs provides avenues for prophylactic or therapeutic intervention against re-emerging MeV. • Measles-specific mAbs were isolated from a human MMR vaccinee, years after vaccination • MAbs recognize four major sites on hemagglutinin (H) and five on the fusion (F) protein • Lead mAbs against H and F exhibit picomolar neutralization via diverse mechanisms • Anti-H and -F mAbs reduce viral loads in vivo , even when given 48 h after infection Acciani, Zyla et al. identify a panel of human monoclonal antibodies against measles virus surface proteins. These antibodies neutralize with picomolar potency, target conserved sites, broadly neutralize diverse strains, and protect animals even after exposure, highlighting opportunities to prevent or treat measles as outbreaks re-emerge.