The Journal of experimental medicine · 2020
Potent human broadly neutralizing antibodies to hepatitis B virus from natural controllers.
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Hehle Verena, Beretta Maxime, Bourgine Maryline, Ait-Goughoulte Malika, Planchais Cyril, Morisse Solen, Vesin Benjamin, Lorin Valérie, Hieu Thierry, Stauffer Andrea, Fiquet Oriane, Dimitrov Jordan D, Michel Marie-Louise, Ungeheuer Marie-Noëlle, Sureau Camille, Pol Stanislas, Di Santo James P, Strick-Marchand Hélène, Pelletier Nadège, Mouquet Hugo
Аннотация
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.