Therapeutic efficacy of CT-P59 against P.1 variant of SARS-CoV-2

Abstract

P.1. or gamma variant also known as the Brazil variant, is one of the variants of concern (VOC) which appears to have high transmissibility and mortality. To explore the potency of the CT-P59 monoclonal antibody against P.1 variant, we tried to conduct binding affinity, in vitro neutralization, and in vivo animal tests. In in vitro assays revealed that CT-P59 is able to neutralize P.1 variant in spite of reduction in its binding affinity against a RBD (receptor binding domain) mutant protein including K417T/E484K/N501Y and neutralizing activity against P.1 pseudoviruses and live viruses. In contrast, in vivo hACE2 (human angiotensin-converting enzyme 2)-expressing TG (transgenic) mouse challenge experiment demonstrated that a clinically relevant or lower dosages of CT-P59 is capable of lowering viral loads in the respiratory tract and alleviates symptoms such as body weight losses and survival rates. Therefore, a clinical dosage of CT-P59 could compensate for reduced in vitro antiviral activity in P.1-infected mice, implying that CT-P59 has therapeutic potency for COVID-19 patients infected with P.1 variant.HighlightsCT-P59 could bind to and neutralize P.1 variant, but CT-P59 showed reduced susceptibility in in vitro tests.The clinical dosage of CT-P59 demonstrated in vivo therapeutic potency against P.1 variants in hACE2-expressing mice challenge study.CT-P59 ameliorates their body weight loss and prevents the lethality in P.1 variant-infected mice.

Potent neutralizing anti-SARS-CoV-2 human antibodies cure infection with SARS-CoV-2 variants in hamster model

“…Tixagevimab did not show activity against omicron either, while cilgavimab retained some activity (albeit 15-fold lower), resulting in a 42-fold reduction of the activity of the tixagevimab/cilgavimabb cocktail against omicron. On the other hand, sotrovimab and bebtelovimab are still retaining activity against beta, delta, and omicron (Cameroni et al, 2021;Corti et al, 2021;Ryu and Kang, et al, 2021;Ryu and Song, et al, 2021;Hoffmann et al, 2021;Planas et al, 2021;Westendorf et al, 2022;Ju et al, 2022;Li et al, 2022;Touret et al, 2022). This demonstrates that several of the commercially available therapeutic mAbs lose their activity against multiple SARS-CoV-2 variants of concern (VoC).…”