| Literature DB >> 32504577 |
Qiao Wang1, Eleftherios Michailidis2, Yingpu Yu2, Zijun Wang3, Arlene M Hurley3, Deena A Oren4, Christian T Mayer3, Anna Gazumyan3, Zhenmi Liu5, Yunjiao Zhou6, Till Schoofs3, Kai-Hui Yao3, Jan P Nieke3, Jianbo Wu6, Qingling Jiang5, Chenhui Zou7, Mohanmmad Kabbani2, Corrine Quirk2, Thiago Oliveira3, Kalsang Chhosphel3, Qianqian Zhang6, William M Schneider2, Cyprien Jahan2, Tianlei Ying6, Jill Horowitz3, Marina Caskey3, Mila Jankovic3, Davide F Robbiani3, Yumei Wen6, Ype P de Jong8, Charles M Rice2, Michel C Nussenzweig9.
Abstract
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.Entities:
Keywords: Hepatitis B infection; broadly neutralizing antibodies; crystal structure; elite neutralizing activity; escape mutations; humanized mice; passive immunotherapy; prophylaxis
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Year: 2020 PMID： 32504577 PMCID： PMC8182833 DOI： 10.1016/j.chom.2020.05.010
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023