A Combination of Human Broadly Neutralizing Antibodies against Hepatitis B Virus HBsAg with Distinct Epitopes Suppresses Escape Mutations

Wang, Qiao; Michailidis, Eleftherios; Yu, Yingpu; Wang, Zijun; Hurley, Arlene M.; Oren, Deena A.; Mayer, Christian T.; Gazumyan, Anna; Liu, Zhenmi; Zhou, Yunjiao; Schoofs, Till; Yao, Kai-hui; Nieke, Jan P.; Wu, Jianbo; Jiang, Qingling; Zou, Chenhui; Kabbani, Mohanmmad; Quirk, Corrine; Oliveira, Thiago; Chhosphel, Kalsang; Zhang, Qianqian; Schneider, William M.; Jahan, Cyprien; Ying, Tianlei; Horowitz, Jill; Caskey, Marina; Jankovic, Mila; Robbiani, Davide F.; Wen, Yumei; de Jong, Ype P.; Rice, Charles M.; Nussenzweig, Michel C.

doi:10.1016/j.chom.2020.05.010

Title: A Combination of Human Broadly Neutralizing Antibodies against Hepatitis B Virus HBsAg with Distinct Epitopes Suppresses Escape Mutations

Journal Article · Fri Jun 05 00:00:00 EDT 2020 · Cell Host & Microbe

DOI:https://doi.org/10.1016/j.chom.2020.05.010· OSTI ID:1829849

Wang, Qiao ^[1]; Michailidis, Eleftherios ^[2]; Yu, Yingpu ^[2]; Wang, Zijun ^[3]; Hurley, Arlene M. ^[3]; Oren, Deena A. ^[4]; Mayer, Christian T. ^[3]; Gazumyan, Anna ^[3]; Liu, Zhenmi ^[5]; Zhou, Yunjiao ^[1]; Schoofs, Till ^[3]; Yao, Kai-hui ^[3]; Nieke, Jan P. ^[3]; Wu, Jianbo ^[1]; Jiang, Qingling ^[5]; Zou, Chenhui ^[6]; Kabbani, Mohanmmad ^[2]; Quirk, Corrine ^[2]; Oliveira, Thiago ^[3]; Chhosphel, Kalsang ^[3] more »

Fudan Univ., Shanghai (China). Key Lab. of Medical Molecular Virology (MOE/NHC/CAMS). School of Basic Medical Sciences. Shanghai Medical College
Rockefeller Univ., New York, NY (United States). Lab. of Virology and Infectious Disease
Rockefeller Univ., New York, NY (United States). Lab. of Molecular Immunology
Rockefeller Univ., New York, NY (United States). Structural Biology Resource Center
Sichuan Univ., Chengdu (China). West China School of Public Health. West China Hospital
Rockefeller Univ., New York, NY (United States). Lab. of Virology and Infectious Disease; Weill Cornell Medicine, New York, NY (United States). Division of Gastroenterology and Hepatology
Rockefeller Univ., New York, NY (United States). Lab. of Molecular Immunology. Howard Hughes Medical Inst.

Although there is no effective cure for chronic hepatitis B virus (HBV) infection, antibodies are protective and correlate with recovery from infection. To examine the human antibody response to HBV, we screened 124 vaccinated and 20 infected, spontaneously recovered individuals. The selected individuals produced shared clones of broadly neutralizing antibodies (bNAbs) that targeted 3 non-overlapping epitopes on the HBV S antigen (HBsAg). Single bNAbs protected humanized mice against infection but selected for resistance mutations in mice with prior established infection. In contrast, infection was controlled by a combination of bNAbs targeting non-overlapping epitopes with complementary sensitivity to mutations that commonly emerge during human infection. The co-crystal structure of one of the bNAbs with an HBsAg peptide epitope revealed a stabilized hairpin loop. This structure, which contains residues frequently mutated in clinical immune escape variants, provides a molecular explanation for why immunotherapy for HBV infection may require combinations of complementary bNAbs.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1829849

Alternate ID(s):: OSTI ID: 1703989

Journal Information:: Cell Host & Microbe, Vol. 28, Issue 2; ISSN 1931-3128

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Detection of Additional Antigenic Determinants of Hepatitis B Antigen Bancroft, William H.; Mundon, Francis K.; Russell, Philip K. The Journal of Immunology, Vol. 109, Issue 4 https://doi.org/10.4049/jimmunol.109.4.842	journal	October 1972

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