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Updated: Nov 9, 2025
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease
Marianna Agudelo1, Martin Palus2,3, Jennifer R Keeffe4
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.
Abstract:
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.
Insights
Human antibodies offer protection against tick-borne encephalitis virus (TBEV). The most potent neutralizing antibodies, effective against multiple tick-borne flaviviruses, were identified in individuals who recovered from natural TBEV infection.
Area of Science:
- Virology
- Immunology
- Public Health
Background:
- Tick-borne encephalitis virus (TBEV) is an emerging pathogen causing severe neurological disease.
- No specific antiviral treatment exists for TBEV infections.
- Understanding the human antibody response is crucial for developing effective therapies.
Purpose of the Study:
- To characterize the human neutralizing antibody response to TBEV following natural infection and vaccination.
- To identify potent neutralizing antibodies and their targets.
- To evaluate the cross-neutralizing potential of these antibodies against related flaviviruses.
Main Methods:
- Analysis of memory B cell clones from infected and vaccinated individuals.
- Quantification of antibody neutralization potency (IC50).
- Structural analysis of antibody-epitope interactions.
- In vivo efficacy studies in a mouse model of TBEV infection.
Main Results:
- Memory B cells produced closely related anti-envelope domain III (EDIII) antibodies in both groups.
- Individuals recovered from natural infection produced highly potent neutralizing antibodies (IC50 < 1 ng/ml).
- These antibodies neutralized a range of tick-borne flaviviruses and recognized a conserved epitope on EDIII.
- Prophylactic or early therapeutic antibody administration showed efficacy in a lethal TBEV mouse model.
Conclusions:
- Naturally acquired TBEV infection elicits potent, broadly cross-neutralizing human antibodies targeting a conserved EDIII epitope.
- These antibodies represent promising candidates for passive immunotherapy against TBEV and related flaviviruses.
- Further development of these antibodies could lead to novel prophylactic or therapeutic strategies for tick-borne flavivirus infections.
