Potent human broadly neutralizing antibodies to hepatitis B virus from natural controllers.
Animals
Antibodies, Neutralizing
/ immunology
B-Lymphocytes
/ immunology
Cross Reactions
/ immunology
Enzyme-Linked Immunosorbent Assay
Epitopes
/ immunology
Flow Cytometry
Hepatitis B
/ immunology
Hepatitis B Surface Antigens
/ immunology
Hepatitis B Vaccines
/ immunology
Hepatitis B virus
/ immunology
Hepatitis B, Chronic
/ immunology
Humans
Immunologic Memory
/ immunology
Mice
Neutralization Tests
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
05 10 2020
05 10 2020
Historique:
received:
29
04
2020
revised:
03
06
2020
accepted:
04
06
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
11
3
2021
Statut:
ppublish
Résumé
Rare individuals can naturally clear chronic hepatitis B virus (HBV) infection and acquire protection from reinfection as conferred by vaccination. To examine the protective humoral response against HBV, we cloned and characterized human antibodies specific to the viral surface glycoproteins (HBsAg) from memory B cells of HBV vaccinees and controllers. We found that human HBV antibodies are encoded by a diverse set of immunoglobulin genes and recognize various conformational HBsAg epitopes. Strikingly, HBsAg-specific memory B cells from natural controllers mainly produced neutralizing antibodies able to cross-react with several viral genotypes. Furthermore, monotherapy with the potent broadly neutralizing antibody Bc1.187 suppressed viremia in vivo in HBV mouse models and led to post-therapy control of the infection in a fraction of animals. Thus, human neutralizing HBsAg antibodies appear to play a key role in the spontaneous control of HBV and represent promising immunotherapeutic tools for achieving HBV functional cure in chronically infected humans.
Identifiants
pubmed: 32579155
pii: 151888
doi: 10.1084/jem.20200840
pmc: PMC7537403
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Epitopes
0
Hepatitis B Surface Antigens
0
Hepatitis B Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 Hehle et al.
Déclaration de conflit d'intérêts
Disclosures: V. Hehle reported a patent to anti-HBV antibodies and methods of use, pending. M. Beretta reported a patent to anti-HBV antibodies and methods of use, pending. M. Bourgine reported a patent to anti-HBV antibodies and methods of use, pending. M. Ait-Goughoulte reported a patent planned on the antibodies pending, "Roche." S. Pol reported personal fees from Gilead, Abbvie, BMS, Janssen, and Roche outside the submitted work. H. Strick-Marchand reported a patent to human neutralizing HBV antibodies and their use thereof, pending. N. Pelletier reported personal fees from Hoffmann-La Roche outside the submitted work; in addition, N. Pelletier had a patent planned to be submitted, pending "Roche Innovation Center Basel." H. Mouquet reported grants from Institut Roche during the conduct of the study; in addition, H. Mouquet had a patent to anti-HBV antibodies and methods of use, pending. No other disclosures were reported.
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