Potent human broadly neutralizing antibodies to hepatitis B virus from natural controllers
Verena Hehle1,2*, Maxime Beretta1,2*, Maryline Bourgine3, Malika Ait-Goughoulte4, Cyril Planchais1,2, Solen Morisse3, Benjamin Vesin3, Valérie Lorin1,2, Thierry Hieu1,2, Andrea Stauffer4, Oriane Fiquet5,6, Jordan D. Dimitrov7, Marie-Louise Michel8, Marie-No¨elle Ungeheuer9, Camille Sureau10, Stanislas Pol6,11, James P. Di Santo5,6, H´elène Strick-Marchand5,6**, Nadège Pelletier4**, and Hugo Mouquet1,2
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.
Published in Journal of Experimental Medicine