The neutralization potency of anti-SARS-CoV-2 therapeutic human monoclonal antibodies is retained against viral variants

Efi Makdasi, Anat Zvi, Ron Alcalay, Tal Noy-Porat, Eldar Peretz, Adva Mechaly, Yinon Levy, Eyal Epstein, Theodor Chitlaru, Ariel Tennenhouse, Moshe Aftalion, David Gur, Nir Paran, Hadas Tamir, Oren Zimhony, Shay Weiss, Michal Mandelboim, Ella Mendelson, Neta Zuckerman, Ital NemetLimor Kliker, Shmuel Yitzhaki, Shmuel C. Shapira, Tomer Israely, Sarel J. Fleishman, Ohad Mazor, Ronit Rosenfeld

Research output: Contribution to journalArticlepeer-review

Abstract

A wide range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing monoclonal antibodies (mAbs) have been reported, most of which target the spike glycoprotein. Therapeutic implementation of these antibodies has been challenged by emerging SARS-CoV-2 variants harboring mutated spike versions. Consequently, re-assessment of previously identified mAbs is of high priority. Four previously selected mAbs targeting non-overlapping epitopes are now evaluated for binding potency to mutated RBD versions, reported to mediate escape from antibody neutralization. In vitro neutralization potencies of these mAbs, and two NTD-specific mAbs, are evaluated against two frequent SARS-CoV-2 variants of concern, the B.1.1.7 Alpha and the B.1.351 Beta. Furthermore, we demonstrate therapeutic potential of three selected mAbs by treatment of K18-human angiotensin-converting enzyme 2 (hACE2) transgenic mice 2 days post-infection with each virus variant. Thus, despite the accumulation of spike mutations, the highly potent MD65 and BL6 mAbs retain their ability to bind the prevalent viral mutants, effectively protecting against B.1.1.7 and B.1.351 variants.

Original languageEnglish
Article number109679
JournalCell Reports
Volume36
Issue number10
Early online date21 Aug 2021
DOIs
StatePublished - 7 Sep 2021

Keywords

  • K18-hACE2 mice
  • SARS-CoV-2
  • VOCs
  • escape mutants
  • mAbs
  • neutralizing antibodies
  • variants

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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