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

iScience. 2022 Sep 16;25(9):104935. doi: 10.1016/j.isci.2022.104935. Epub 2022 Aug 13.

Authors

Abigael E Chaouat¹, Ilija Brizic², Paola Kucan Brlic², Nofar Atari³, Limor Kliker³, Or Alfi¹, Michal Mandelboim^{3

4}, Dana Wolf^{1

5}, Laith Tafish¹, Inbal Kol¹, Stipan Jonjic², Ofer Mandelboim¹

Affiliations

¹ The Concern Foundation Laboratories at the Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), The Hebrew University Hadassah Medical School, Ein Karem, Jerusalem 9112001, Israel.
² Center for Proteomics University of Rijeka, Faculty of Medicine, Brace Branchetta 20, 51000 Rijeka, Croatia.
³ Central Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Sheba Medical Center Hospital- Tel Hashomer, Ramat Gan 52621, Israel.
⁴ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
⁵ The Hebrew University, Hadassah Medical Center, Ein Karem, Jerusalem 9112001, Israel.

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.

Keywords: Health sciences; immune response; immunology; virology.