Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity
Arlene M. Hurley,
Deena A. Oren,
Christian T. Mayer,
Jan P. Nieke,
William M. Schneider,
Davide F. Robbiani,
Ype P de Jong,
Charles M. Rice,
Michel C. Nussenzweig
Posted 05 Mar 2020
bioRxiv DOI: 10.1101/2020.03.04.976159
Posted 05 Mar 2020
Although there is no effective cure for chronic hepatitis B virus (HBV) infection, antibodies are protective and constitute clinical correlates of recovery from infection. To examine the human neutralizing antibody response to HBV in elite neutralizers we screened 144 individuals. The top 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 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 a peptide epitope containing residues frequently mutated in human immune escape variants revealed a loop anchored by oppositely charged residues. The structure provides a molecular explanation for why immunotherapy for HBV infection may require combinations of complementary bNAbs.
- Downloaded 376 times
- Download rankings, all-time:
- Site-wide: 51,794 out of 105,802
- In immunology: 1,511 out of 3,257
- Year to date:
- Site-wide: 13,224 out of 105,802
- Since beginning of last month:
- Site-wide: 26,321 out of 105,802
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!