An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses

Lihong Liu; Sho Iketani; Yicheng Guo; Eswar R. Reddem; Ryan G. Casner; Manoj S. Nair; Jian Yu; Jasper F.W. Chan; Maple Wang; Gabriele Cerutti; Zhiteng Li; Nicholas C. Morano; Candace D. Castagna; Laura Corredor; Hin Chu; Shuofeng Yuan; Vincent Kwok Man Poon; Chris Chun Sing Chan; Zhiwei Chen; Yang Luo; Marcus Cunningham; Alejandro Chavez; Michael T. Yin; David S. Perlin; Moriya Tsuji; Kwok Yung Yuen; Peter D. Kwong; Zizhang Sheng; Yaoxing Huang; Lawrence Shapiro; David D. Ho

doi:10.1126/scitranslmed.abn6859

An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses

Lihong Liu, Sho Iketani, Yicheng Guo, Eswar R. Reddem, Ryan G. Casner, Manoj S. Nair, Jian Yu, Jasper F.W. Chan, Maple Wang, Gabriele Cerutti, Zhiteng Li, Nicholas C. Morano, Candace D. Castagna, Laura Corredor, Hin Chu, Shuofeng Yuan, Vincent Kwok Man Poon, Chris Chun Sing Chan, Zhiwei Chen, Yang LuoMarcus Cunningham, Alejandro Chavez, Michael T. Yin, David S. Perlin, Moriya Tsuji, Kwok Yung Yuen, Peter D. Kwong, Zizhang Sheng, Yaoxing Huang, Lawrence Shapiro, David D. Ho

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptorbinding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

Original language	English
Article number	eabn6859
Journal	Science Translational Medicine
Volume	14
Issue number	646
DOIs	https://doi.org/10.1126/scitranslmed.abn6859
Publication status	Published - May 25 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

ASJC Scopus Subject Areas

General Medicine

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10.1126/scitranslmed.abn6859

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Liu, L., Iketani, S., Guo, Y., Reddem, E. R., Casner, R. G., Nair, M. S., Yu, J., Chan, J. F. W., Wang, M., Cerutti, G., Li, Z., Morano, N. C., Castagna, C. D., Corredor, L., Chu, H., Yuan, S., Poon, V. K. M., Chan, C. C. S., Chen, Z., ... Ho, D. D. (2022). An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses. Science Translational Medicine, 14(646), Article eabn6859. https://doi.org/10.1126/scitranslmed.abn6859

Liu, L, Iketani, S, Guo, Y, Reddem, ER, Casner, RG, Nair, MS, Yu, J, Chan, JFW, Wang, M, Cerutti, G, Li, Z, Morano, NC, Castagna, CD, Corredor, L, Chu, H, Yuan, S, Poon, VKM, Chan, CCS, Chen, Z, Luo, Y, Cunningham, M, Chavez, A, Yin, MT, Perlin, DS, Tsuji, M, Yuen, KY, Kwong, PD, Sheng, Z, Huang, Y, Shapiro, L & Ho, DD 2022, 'An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses', Science Translational Medicine, vol. 14, no. 646, eabn6859. https://doi.org/10.1126/scitranslmed.abn6859

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abstract = "The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptorbinding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.",

author = "Lihong Liu and Sho Iketani and Yicheng Guo and Reddem, {Eswar R.} and Casner, {Ryan G.} and Nair, {Manoj S.} and Jian Yu and Chan, {Jasper F.W.} and Maple Wang and Gabriele Cerutti and Zhiteng Li and Morano, {Nicholas C.} and Castagna, {Candace D.} and Laura Corredor and Hin Chu and Shuofeng Yuan and Poon, {Vincent Kwok Man} and Chan, {Chris Chun Sing} and Zhiwei Chen and Yang Luo and Marcus Cunningham and Alejandro Chavez and Yin, {Michael T.} and Perlin, {David S.} and Moriya Tsuji and Yuen, {Kwok Yung} and Kwong, {Peter D.} and Zizhang Sheng and Yaoxing Huang and Lawrence Shapiro and Ho, {David D.}",

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AU - Iketani, Sho

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AU - Nair, Manoj S.

AU - Yu, Jian

AU - Chan, Jasper F.W.

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AU - Cerutti, Gabriele

AU - Li, Zhiteng

AU - Morano, Nicholas C.

AU - Castagna, Candace D.

AU - Corredor, Laura

AU - Chu, Hin

AU - Yuan, Shuofeng

AU - Poon, Vincent Kwok Man

AU - Chan, Chris Chun Sing

AU - Chen, Zhiwei

AU - Luo, Yang

AU - Cunningham, Marcus

AU - Chavez, Alejandro

AU - Yin, Michael T.

AU - Perlin, David S.

AU - Tsuji, Moriya

AU - Yuen, Kwok Yung

AU - Kwong, Peter D.

AU - Sheng, Zizhang

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AU - Shapiro, Lawrence

AU - Ho, David D.

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N2 - The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptorbinding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

AB - The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptorbinding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

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An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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