%0 Journal Article %T Potent human broadly neutralizing antibodies to hepatitis B virus from natural controllers %+ Immunologie humorale - Humoral Immunology %+ Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology %+ F. Hoffmann-La Roche [Basel] %+ Immunité Innée - Innate Immunity %+ Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)) %+ Institut Pasteur [Paris] (IP) %+ Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB) %+ Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)) %+ Centre de Recherche Translationnelle - Center for Translational Science (CRT) %A Hehle, Verena %A Beretta, Maxime %A Bourgine, M %A Ait-Goughoulte, Malika %A Planchais, Cyril %A Morisse, Solen %A Vesin, Benjamin %A Lorin, Valérie %A Hieu, Thierry %A Stauffer, Andrea %A Fiquet, Oriane %A Dimitrov, Jordan, D. %A Michel, Marie-Louise %A Ungeheuer, Marie-Noëlle %A Sureau, Camille %A Pol, Stanislas %A Di Santo, James, P. %A Strick-Marchand, Hélène %A Pelletier, Nadège %A Mouquet, Hugo %Z H. Mouquet received core grants from the G5 Institut Pasteur Program, the Milieu Intérieur Program (ANR-10-LABX-69-01) and INSERM. This work was funded by Institut Roche. V. Hehle and M. Beretta were supported by postdoctoral fellowships from Roche. V. Hehle and T. Hieu were also supported by the European Research Council–Seventh Framework Program (ERC-2013-StG 337146). H. Strick-Marchand was supported by the Institut Pasteur and Agence Nationale de Recherches sur le Sida et les Hépatites Virales (2016-16365, 2019-19241). %< avec comité de lecture %@ 0022-1007 %J Journal of Experimental Medicine %I Rockefeller University Press %V 217 %N 10 %P e20200840 %8 2020-06-24 %D 2020 %R 10.1084/jem.20200840 %M 32579155 %Z Life Sciences [q-bio]/Immunology/Immunotherapy %Z Life Sciences [q-bio]/Immunology/VaccinologyJournal articles %X 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. %G English %Z We are grateful to members of the Center for Translational Sciences (Institut Pasteur), Cassandre Von Platen (Clinical core) for the preparation of the RAPIVIB protocol, and Gloria Morizot (Investigation Clinique et Accès aux Ressources Biologiques) for collecting biological samples and associated personal data. We also thank Sandrine Schmutz, Sophie Novault (UTechS CB, Center for Translational Sciences, Institut Pasteur), and Ayrin Kök for their technical help with single cell sorting, and Dr. J. Aguilar (Center for Genetic Engineering and Biotechnology, Havana, Cuba) for providing us with the purified adw HBsAg particles. %2 https://pasteur.hal.science/pasteur-03242779/document %2 https://pasteur.hal.science/pasteur-03242779/file/jem_20200840.pdf %L pasteur-03242779 %U https://pasteur.hal.science/pasteur-03242779 %~ INSERM %~ PASTEUR %~ EPHE %~ UNIV-AG %~ AFRIQ %~ OPENAIRE %~ CORDELIERS %~ ATP-IMMUN %~ PSL %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ SU-SCIENCES %~ TEST-DEV %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SANTE %~ UP-SCIENCES %~ EPHE-PSL %~ SU-TI %~ ANR %~ ALLIANCE-SU %~ HUMORAL-IMMUNOLOGY %~ U1222