Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity
SUMMARY 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..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 28. Sept. Zur Gesamtaufnahme - year:2023 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Qiao [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1101/2020.03.04.976159 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI000755982 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI000755982 | ||
| 003 | DE-627 | ||
| 005 | 20231205150523.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200313s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2020.03.04.976159 |2 doi | |
| 035 | |a (DE-627)XBI000755982 | ||
| 035 | |a (biorXiv)10.1101/2020.03.04.976159 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Qiao |e verfasserin |0 (orcid)0000-0001-6416-1733 |4 aut | |
| 245 | 1 | 0 | |a Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a SUMMARY 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. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Michailidis, Eleftherios |0 (orcid)0000-0002-9907-4346 |4 aut | |
| 700 | 1 | |a Yu, Yingpu |4 aut | |
| 700 | 1 | |a Wang, Zijun |4 aut | |
| 700 | 1 | |a Hurley, Arlene M. |4 aut | |
| 700 | 1 | |a Oren, Deena A. |4 aut | |
| 700 | 1 | |a Mayer, Christian T. |0 (orcid)0000-0002-0256-9650 |4 aut | |
| 700 | 1 | |a Gazumyan, Anna |4 aut | |
| 700 | 1 | |a Liu, Zhenmi |0 (orcid)0000-0003-0840-1071 |4 aut | |
| 700 | 1 | |a Zhou, Yunjiao |4 aut | |
| 700 | 1 | |a Schoofs, Till |4 aut | |
| 700 | 1 | |a Yao, Kai-hui |4 aut | |
| 700 | 1 | |a Nieke, Jan P. |4 aut | |
| 700 | 1 | |a Wu, Jianbo |4 aut | |
| 700 | 1 | |a Jiang, Qingling |4 aut | |
| 700 | 1 | |a Zou, Chenhui |4 aut | |
| 700 | 1 | |a Kabbani, Mohanmmad |4 aut | |
| 700 | 1 | |a Quirk, Corrine |4 aut | |
| 700 | 1 | |a Oliveira, Thiago |4 aut | |
| 700 | 1 | |a Chhosphel, Kalsang |4 aut | |
| 700 | 1 | |a Zhang, Qianqian |4 aut | |
| 700 | 1 | |a Schneider, William M. |4 aut | |
| 700 | 1 | |a Jahan, Cyprien |4 aut | |
| 700 | 1 | |a Ying, Tianlei |0 (orcid)0000-0002-9597-2843 |4 aut | |
| 700 | 1 | |a Horowitz, Jill |4 aut | |
| 700 | 1 | |a Caskey, Marina |4 aut | |
| 700 | 1 | |a Jankovic, Mila |4 aut | |
| 700 | 1 | |a Robbiani, Davide F. |0 (orcid)0000-0001-7379-3484 |4 aut | |
| 700 | 1 | |a Wen, Yumei |4 aut | |
| 700 | 1 | |a de Jong, Ype P. |4 aut | |
| 700 | 1 | |a Rice, Charles M. |4 aut | |
| 700 | 1 | |a Nussenzweig, Michel C. |0 (orcid)0000-0003-0592-8564 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2023) vom: 28. Sept. |
| 773 | 1 | 8 | |g year:2023 |g day:28 |g month:09 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.03.04.976159 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 951 | |a AR | ||
| 952 | |j 2023 |b 28 |c 09 | ||