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

Ryu, Dong-Kyun; Kang, Bobin; Woo, Sun-Je; Lee, Min-Ho; Tijsma, Aloys SL; Noh, Hanmi; Kim, Jong-In; Seo, Ji-Min; Kim, Cheolmin; Kim, Minsoo; Yang, Eunji; Lim, Gippeum; Kim, Seong-Gyu; Eo, Su-Kyeong; Choi, Jung-ah; Oh, Sang-Seok; Nuijten, Patricia M; Song, Manki; Chung, Hyo-Young; van Baalen, Carel A; Kwon, Ki-Sung; Lee, Soo-Young

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. Highlights CT-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.