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Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant

View ORCID ProfileDong-Kyun Ryu, Rina Song, Minsoo Kim, Young-Il Kim, Cheolmin Kim, Jong-In Kim, Ki-Sung Kwon, Aloys SL Tijsma, Patricia M Nuijten, Carel A van Baalen, Tandile Hermanus, Prudence Kgagudi, Thandeka Gwete-Moyo, Penny L Moore, View ORCID ProfileYoung Ki Choi, View ORCID ProfileSoo-Young Lee
doi: https://doi.org/10.1101/2021.04.27.441707
Dong-Kyun Ryu
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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Rina Song
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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Minsoo Kim
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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Young-Il Kim
2College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea
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Cheolmin Kim
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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Jong-In Kim
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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Ki-Sung Kwon
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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Aloys SL Tijsma
3Viroclinics Biosciences, Rotterdam, The Netherlands
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Patricia M Nuijten
3Viroclinics Biosciences, Rotterdam, The Netherlands
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Carel A van Baalen
3Viroclinics Biosciences, Rotterdam, The Netherlands
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Tandile Hermanus
4National Institute for Communicable Disease, Johannesburg of the National Health Laboratory Services, South African
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Prudence Kgagudi
4National Institute for Communicable Disease, Johannesburg of the National Health Laboratory Services, South African
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Thandeka Gwete-Moyo
4National Institute for Communicable Disease, Johannesburg of the National Health Laboratory Services, South African
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Penny L Moore
4National Institute for Communicable Disease, Johannesburg of the National Health Laboratory Services, South African
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Young Ki Choi
2College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea
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Soo-Young Lee
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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  • For correspondence: sooyoung.lee@celltrion.com
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Abstract

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.

Highlights

  • CT-P59 significantly inhibit B.1.1.7 variant to a similar extent as to wild type virus

  • CT-P59 showed reduced potency against the B.1.351 variant in in vitro studies

  • Therapeutic dosage of CT-P59 showed in vivo neutralizing potency against B.1.351 in ferret challenge study.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 28, 2021.
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Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant
Dong-Kyun Ryu, Rina Song, Minsoo Kim, Young-Il Kim, Cheolmin Kim, Jong-In Kim, Ki-Sung Kwon, Aloys SL Tijsma, Patricia M Nuijten, Carel A van Baalen, Tandile Hermanus, Prudence Kgagudi, Thandeka Gwete-Moyo, Penny L Moore, Young Ki Choi, Soo-Young Lee
bioRxiv 2021.04.27.441707; doi: https://doi.org/10.1101/2021.04.27.441707
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Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant
Dong-Kyun Ryu, Rina Song, Minsoo Kim, Young-Il Kim, Cheolmin Kim, Jong-In Kim, Ki-Sung Kwon, Aloys SL Tijsma, Patricia M Nuijten, Carel A van Baalen, Tandile Hermanus, Prudence Kgagudi, Thandeka Gwete-Moyo, Penny L Moore, Young Ki Choi, Soo-Young Lee
bioRxiv 2021.04.27.441707; doi: https://doi.org/10.1101/2021.04.27.441707

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