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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 is known about the human antibody response to infection. Here, we report on the human neutralizing...

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Autores principales: Agudelo, Marianna, Palus, Martin, Keeffe, Jennifer R., Bianchini, Filippo, Svoboda, Pavel, Salát, Jiří, Peace, Avery, Gazumyan, Anna, Cipolla, Melissa, Kapoor, Tania, Guidetti, Francesca, Yao, Kai-Hui, Elsterová, Jana, Teislerová, Dana, Chrdle, Aleš, Hönig, Václav, Oliveira, Thiago, West, Anthony P., Lee, Yu E., Rice, Charles M., MacDonald, Margaret R., Bjorkman, Pamela J., Růžek, Daniel, Robbiani, Davide F., Nussenzweig, Michel C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040517/
https://www.ncbi.nlm.nih.gov/pubmed/33831141
http://dx.doi.org/10.1084/jem.20210236
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author Agudelo, Marianna
Palus, Martin
Keeffe, Jennifer R.
Bianchini, Filippo
Svoboda, Pavel
Salát, Jiří
Peace, Avery
Gazumyan, Anna
Cipolla, Melissa
Kapoor, Tania
Guidetti, Francesca
Yao, Kai-Hui
Elsterová, Jana
Teislerová, Dana
Chrdle, Aleš
Hönig, Václav
Oliveira, Thiago
West, Anthony P.
Lee, Yu E.
Rice, Charles M.
MacDonald, Margaret R.
Bjorkman, Pamela J.
Růžek, Daniel
Robbiani, Davide F.
Nussenzweig, Michel C.
author_facet Agudelo, Marianna
Palus, Martin
Keeffe, Jennifer R.
Bianchini, Filippo
Svoboda, Pavel
Salát, Jiří
Peace, Avery
Gazumyan, Anna
Cipolla, Melissa
Kapoor, Tania
Guidetti, Francesca
Yao, Kai-Hui
Elsterová, Jana
Teislerová, Dana
Chrdle, Aleš
Hönig, Václav
Oliveira, Thiago
West, Anthony P.
Lee, Yu E.
Rice, Charles M.
MacDonald, Margaret R.
Bjorkman, Pamela J.
Růžek, Daniel
Robbiani, Davide F.
Nussenzweig, Michel C.
author_sort Agudelo, Marianna
collection PubMed
description 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 IC(50)s 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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spelling pubmed-80405172021-05-05 Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease Agudelo, Marianna Palus, Martin Keeffe, Jennifer R. Bianchini, Filippo Svoboda, Pavel Salát, Jiří Peace, Avery Gazumyan, Anna Cipolla, Melissa Kapoor, Tania Guidetti, Francesca Yao, Kai-Hui Elsterová, Jana Teislerová, Dana Chrdle, Aleš Hönig, Václav Oliveira, Thiago West, Anthony P. Lee, Yu E. Rice, Charles M. MacDonald, Margaret R. Bjorkman, Pamela J. Růžek, Daniel Robbiani, Davide F. Nussenzweig, Michel C. J Exp Med Article 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 IC(50)s 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. Rockefeller University Press 2021-04-08 /pmc/articles/PMC8040517/ /pubmed/33831141 http://dx.doi.org/10.1084/jem.20210236 Text en © 2021 Agudelo et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Agudelo, Marianna
Palus, Martin
Keeffe, Jennifer R.
Bianchini, Filippo
Svoboda, Pavel
Salát, Jiří
Peace, Avery
Gazumyan, Anna
Cipolla, Melissa
Kapoor, Tania
Guidetti, Francesca
Yao, Kai-Hui
Elsterová, Jana
Teislerová, Dana
Chrdle, Aleš
Hönig, Václav
Oliveira, Thiago
West, Anthony P.
Lee, Yu E.
Rice, Charles M.
MacDonald, Margaret R.
Bjorkman, Pamela J.
Růžek, Daniel
Robbiani, Davide F.
Nussenzweig, Michel C.
Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease
title Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease
title_full Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease
title_fullStr Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease
title_full_unstemmed Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease
title_short Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease
title_sort broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040517/
https://www.ncbi.nlm.nih.gov/pubmed/33831141
http://dx.doi.org/10.1084/jem.20210236
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