Potently neutralizing and protective human monoclonal antibodies against the measles fusion protein trimer

Measles remains a significant source of morbidity and mortality globally. There are currently no licensed treatments for patients at high risk of severe disease. There is limited knowledge about the human antibody response to a measles infection or vaccination or the structural determinants of antibody-mediated neutralization on the measles virus surface hemagglutinin (H) and fusion (F) glycoproteins. Here, we describe a panel of human monoclonal antibodies isolated from individuals who had been naturally infected with the measles virus. Several antibodies that recognized a prefusion-stabilized F protein potently neutralized the virus in vitro. We determined the structural basis of molecular recognition and virus neutralization using cryo-electron microscopy (cryo-EM) for two antibodies that recognize distinct sites of the F protein, MeV-15 and MeV-104. These antibodies also strongly inhibited viral replication in vivo when administered prophylactically in a murine transgenic model and when administered therapeutically in a cotton rat model of established infection.