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

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

A wide range of SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) were 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-hACE2 transgenic mice two 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.