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

M. Agudelo, M. Palus, JR. Keeffe, F. Bianchini, P. Svoboda, J. Salát, A. Peace, A. Gazumyan, M. Cipolla, T. Kapoor, F. Guidetti, KH. Yao, J. Elsterová, D. Teislerová, A. Chrdle, V. Hönig, T. Oliveira, AP. West, YE. Lee, CM. Rice, MR. MacDonald,...

. 2021 ; 218 (5) : . [pub] 20210503

Language English Country United States

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.

Persistent link   https://www.medvik.cz/link/bmc22004369

Grant support
R01 AI037526 NIAID NIH HHS - United States
P01 AI138938 NIAID NIH HHS - United States
U19 AI111825 NIAID NIH HHS - United States
UM1 AI100663 NIAID NIH HHS - United States
T32 AI070084 NIAID NIH HHS - United States
Howard Hughes Medical Institute - United States
U19 AI057229 NIAID NIH HHS - United States
UL1 TR001866 NCATS NIH HHS - United States
R01 AI124690 NIAID NIH HHS - United States

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 is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI-EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.

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$a 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 is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI-EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.
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