Nature, volume 595, issue 7866, pages 278-282
Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants
Jianliang Xu
1
,
Kai Xu
2, 3
,
Seolkyoung Jung
1
,
ANDREA CONTE
1
,
Jenna Lieberman
1
,
Frauke Muecksch
4
,
Julio C.C. Lorenzi
5
,
Solji Park
1
,
Fabian Schmidt
4
,
Zijun Wang
5
,
Yaoxing Huang
6
,
Yang Luo
6
,
Manoj Kumar Mohan Nair
6
,
Pengfei Wang
6
,
Jonathan E. Schulz
7
,
Lino Tessarollo
8
,
Tatsiana Bylund
2
,
Gwo-Yu Chuang
2
,
Adam S Olia
2
,
Tyler Stephens
9
,
I-Ting Teng
2
,
Yaroslav Tsybovsky
9
,
Tongqing ZHOU
2
,
Vincent J. Munster
7
,
David W. T. Ho
6
,
Theodora Hatziioannou
4
,
Paul D. Bieniasz
4, 10
,
Michel C Nussenzweig
5, 10
,
Peter D. Kwong
2
,
Rafael Casellas
1, 11, 12
8
Mouse Cancer Genetics Program, CCR, NCI, NIH, Frederick, USA
|
10
11
The NIH Regulome Project, NIH, Bethesda, USA
|
12
Center for Cancer Research, NCI, NIH, Bethesda, USA
|
Publication type: Journal Article
Publication date: 2021-06-07
Multidisciplinary
Abstract
Since the start of the COVID-19 pandemic, SARS-CoV-2 has caused millions of deaths worldwide. Although a number of vaccines have been deployed, the continual evolution of the receptor-binding domain (RBD) of the virus has challenged their efficacy. In particular, the emerging variants B.1.1.7, B.1.351 and P.1 (first detected in the UK, South Africa and Brazil, respectively) have compromised the efficacy of sera from patients who have recovered from COVID-19 and immunotherapies that have received emergency use authorization1–3. One potential alternative to avert viral escape is the use of camelid VHHs (variable heavy chain domains of heavy chain antibody (also known as nanobodies)), which can recognize epitopes that are often inaccessible to conventional antibodies4. Here, we isolate anti-RBD nanobodies from llamas and from mice that we engineered to produce VHHs cloned from alpacas, dromedaries and Bactrian camels. We identified two groups of highly neutralizing nanobodies. Group 1 circumvents antigenic drift by recognizing an RBD region that is highly conserved in coronaviruses but rarely targeted by human antibodies. Group 2 is almost exclusively focused to the RBD–ACE2 interface and does not neutralize SARS-CoV-2 variants that carry E484K or N501Y substitutions. However, nanobodies in group 2 retain full neutralization activity against these variants when expressed as homotrimers, and—to our knowledge—rival the most potent antibodies against SARS-CoV-2 that have been produced to date. These findings suggest that multivalent nanobodies overcome SARS-CoV-2 mutations through two separate mechanisms: enhanced avidity for the ACE2-binding domain and recognition of conserved epitopes that are largely inaccessible to human antibodies. Therefore, although new SARS-CoV-2 mutants will continue to emerge, nanobodies represent promising tools to prevent COVID-19 mortality when vaccines are compromised. Multivalent nanobodies against SARS-CoV-2 from mice engineered to produce camelid nanobodies recognize conserved epitopes that are inaccessible to human antibodies and show promise as a strategy for dealing with viral escape mutations.
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Citations by publishers
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- We do not take into account publications without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Xu J. et al. Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants // Nature. 2021. Vol. 595. No. 7866. pp. 278-282.
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Xu J., Xu K., Jung S., CONTE A., Lieberman J., Muecksch F., Lorenzi J. C., Park S., Schmidt F., Wang Z., Huang Y., Luo Y., Mohan Nair M. K., Wang P., Schulz J. E., Tessarollo L., Bylund T., Chuang G., Olia A. S., Stephens T., Teng I., Tsybovsky Y., ZHOU T., Munster V. J., Ho D. W. T., Hatziioannou T., Bieniasz P. D., Nussenzweig M. C., Kwong P. D., Casellas R. Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants // Nature. 2021. Vol. 595. No. 7866. pp. 278-282.
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TY - JOUR
DO - 10.1038/s41586-021-03676-z
UR - https://doi.org/10.1038/s41586-021-03676-z
TI - Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants
T2 - Nature
AU - Xu, Jianliang
AU - Xu, Kai
AU - Jung, Seolkyoung
AU - CONTE, ANDREA
AU - Lieberman, Jenna
AU - Muecksch, Frauke
AU - Lorenzi, Julio C.C.
AU - Park, Solji
AU - Schmidt, Fabian
AU - Wang, Zijun
AU - Huang, Yaoxing
AU - Luo, Yang
AU - Mohan Nair, Manoj Kumar
AU - Wang, Pengfei
AU - Schulz, Jonathan E.
AU - Tessarollo, Lino
AU - Bylund, Tatsiana
AU - Chuang, Gwo-Yu
AU - Olia, Adam S
AU - Stephens, Tyler
AU - Teng, I-Ting
AU - Tsybovsky, Yaroslav
AU - ZHOU, Tongqing
AU - Munster, Vincent J.
AU - Ho, David W. T.
AU - Hatziioannou, Theodora
AU - Bieniasz, Paul D.
AU - Nussenzweig, Michel C
AU - Kwong, Peter D.
AU - Casellas, Rafael
PY - 2021
DA - 2021/06/07 00:00:00
PB - Springer Nature
SP - 278-282
IS - 7866
VL - 595
SN - 0028-0836
SN - 1476-4687
ER -
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@article{2021_Xu,
author = {Jianliang Xu and Kai Xu and Seolkyoung Jung and ANDREA CONTE and Jenna Lieberman and Frauke Muecksch and Julio C.C. Lorenzi and Solji Park and Fabian Schmidt and Zijun Wang and Yaoxing Huang and Yang Luo and Manoj Kumar Mohan Nair and Pengfei Wang and Jonathan E. Schulz and Lino Tessarollo and Tatsiana Bylund and Gwo-Yu Chuang and Adam S Olia and Tyler Stephens and I-Ting Teng and Yaroslav Tsybovsky and Tongqing ZHOU and Vincent J. Munster and David W. T. Ho and Theodora Hatziioannou and Paul D. Bieniasz and Michel C Nussenzweig and Peter D. Kwong and Rafael Casellas},
title = {Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants},
journal = {Nature},
year = {2021},
volume = {595},
publisher = {Springer Nature},
month = {jun},
url = {https://doi.org/10.1038/s41586-021-03676-z},
number = {7866},
pages = {278--282},
doi = {10.1038/s41586-021-03676-z}
}
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Xu, Jianliang, et al. “Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants.” Nature, vol. 595, no. 7866, Jun. 2021, pp. 278-282. https://doi.org/10.1038/s41586-021-03676-z.