Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease

Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little known about the antibody response to infection. Here, we report on neutralizing TBEV in a cohort of infected and vaccinated individuals. Expanded clones memory B cells expressed closely related anti-envelope domain III (EDIII) both groups volunteers. However, most potent antibodies, IC50s below 1 ng/ml, were found only individuals who recovered from natural These also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, Powassan viruses. Structural analysis revealed conserved epitope near lateral ridge EDIII adjoining EDI–EDIII hinge region. Prophylactic or early therapeutic administration was effective at low doses mice lethally TBEV.