Anti-human ACE2 antibody neutralizes and inhibits virus production of SARS-CoV-2 variants of concern

Abigael E. Chaouat; Ilija Brizic; Paola Kucan Brlic; Nofar Atari; Limor Kliker; Or Alfi; Michal Mandelboim; Dana Wolf; Laith Tafish; Inbal Kol; Stipan Jonjic; Ofer Mandelboim

doi:10.1016/j.isci.2022.104935

Anti-human ACE2 antibody neutralizes and inhibits virus production of SARS-CoV-2 variants of concern

Abigael E. Chaouat, Ilija Brizic, Paola Kucan Brlic, Nofar Atari, Limor Kliker, Or Alfi, Michal Mandelboim, Dana Wolf, Laith Tafish, Inbal Kol, Stipan Jonjic, Ofer Mandelboim

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

12 Scopus citations

Abstract

The global pandemic caused by SARS-CoV-2 is a major public health problem. Virus entry occurs via binding to ACE2. Five SARS-CoV-2 variants of concern (VOCs) were reported so far, all having immune escape characteristics. Infection with the current VOC Omicron was noticed in immunized and recovered individuals; therefore, the development of new treatments against VOC infections is urgently needed. Most approved mAbs treatments against SARS-CoV-2 are directed against the spike protein of the original virus and are therefore inefficient against Omicron. Here, we report on the generation of hACE2.16, an anti-ACE2 antibody that recognizes and blocks ACE2-RBD binding without affecting ACE2 enzymatic activity. We demonstrate that hACE2.16 binding to ACE2 does not affect its surface expression and that hACE2.16 blocks infection and virus production of various VOCs including Omicron BA.1 and BA.2. hACE2.16 might, therefore, be an efficient treatment against all VOCs, the current and probably also future ones.

Original language	English
Article number	104935
Journal	iScience
Volume	25
Issue number	9
DOIs	https://doi.org/10.1016/j.isci.2022.104935
State	Published - 16 Sep 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Funding

This work was supported by the following grants awarded to O.M.: the Israel Innovation Authority Kamin grant 62615, the German-Israeli Foundation for Scientific Research and Development grant 1412-414.13/2017, the ICRF professorship grant, the ISF Israel-China grant 2554/18, the MOST-DKFZ grant 3-14931, and the Ministry of Science and Technology grant 3-14764, by Integra Holdings LTD, By the Rothschild Foundation and by the Israel Science Foundation Moked grant 442-18. Graphical abstract was created with BioRender.com. Conceptualization, O.M. and S.J.; Methodology, O.M. S.J. M.M. and D.W.; Investigation, A.E.C. I.B. P.K.B. N.A. L.K. O.A. I.K. and L.T.; Visualization, O.M. and A.E.C.; Funding acquisition, O.M. and S.J.; Project administration, O.M.; Supervision, O.M.; Writing – original draft, O.M. and A.E.C.; Writing – review & editing, O.M. and A.E.C. A patent application has been submitted by Yissum, the Hebrew University Tech Transfer Company, based on these results. This work was supported by the following grants awarded to O.M.: the Israel Innovation Authority Kamin grant 62615 , the German-Israeli Foundation for Scientific Research and Development grant 1412-414.13/2017 , the ICRF professorship grant, the ISF Israel-China grant 2554/18 , the MOST- DKFZ grant 3-14931 , and the Ministry of Science and Technology grant 3-14764 , by Integra Holdings LTD, By the Rothschild Foundation and by the Israel Science Foundation Moked grant 442-18 . Graphical abstract was created with BioRender.com .

Funders	Funder number
ISF Israel-China	2554/18
Integra Holdings LTD
Israel Innovation Authority Kamin	62615
Israel Science Foundation Moked	442-18
MOST-DKFZ
Rothschild Foundation
Israel Cancer Research Fund
German-Israeli Foundation for Scientific Research and Development	1412-414.13/2017
Ministry of Science, Technology and Space	3-14931
Hebrew University of Jerusalem
Ministry of science and technology, Israel	3-14764

Keywords

Health sciences
immune response
immunology
virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.isci.2022.104935

Cite this

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abstract = "The global pandemic caused by SARS-CoV-2 is a major public health problem. Virus entry occurs via binding to ACE2. Five SARS-CoV-2 variants of concern (VOCs) were reported so far, all having immune escape characteristics. Infection with the current VOC Omicron was noticed in immunized and recovered individuals; therefore, the development of new treatments against VOC infections is urgently needed. Most approved mAbs treatments against SARS-CoV-2 are directed against the spike protein of the original virus and are therefore inefficient against Omicron. Here, we report on the generation of hACE2.16, an anti-ACE2 antibody that recognizes and blocks ACE2-RBD binding without affecting ACE2 enzymatic activity. We demonstrate that hACE2.16 binding to ACE2 does not affect its surface expression and that hACE2.16 blocks infection and virus production of various VOCs including Omicron BA.1 and BA.2. hACE2.16 might, therefore, be an efficient treatment against all VOCs, the current and probably also future ones.",

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Anti-human ACE2 antibody neutralizes and inhibits virus production of SARS-CoV-2 variants of concern

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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