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The in vitro and in vivo potency of CT-P59 against Delta and its associated variants of SARS-CoV-2

Dong-Kyun Ryu, Hye-Min Woo, Bobin Kang, Hanmi Noh, Jong-In Kim, Ji-Min Seo, Cheolmin Kim, Minsoo Kim, Jun-Won Kim, Nayoung Kim, Pyeonghwa Jeon, Hansaem Lee, Jeong-Sun Yang, Kyung-Chang Kim, Joo-Yeon Lee, Min-Ho Lee, Sang-Seok Oh, Hyo-Young Chung, Ki-Sung Kwon, View ORCID ProfileSoo-Young Lee
doi: https://doi.org/10.1101/2021.07.23.453472
Dong-Kyun Ryu
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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Hye-Min Woo
2National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea
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Bobin Kang
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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Hanmi Noh
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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Ji-Min Seo
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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Cheolmin Kim
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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Jun-Won Kim
2National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea
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Nayoung Kim
2National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea
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Pyeonghwa Jeon
2National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea
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Hansaem Lee
2National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea
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Jeong-Sun Yang
2National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea
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Kyung-Chang Kim
2National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea
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Joo-Yeon Lee
2National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea
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Min-Ho Lee
3New Drug Development Center, Osong Medical Innovation Foundation, Cheongju, Republic of Korea
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Sang-Seok Oh
3New Drug Development Center, Osong Medical Innovation Foundation, Cheongju, Republic of Korea
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Hyo-Young Chung
3New Drug Development Center, Osong Medical Innovation Foundation, Cheongju, Republic of Korea
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Ki-Sung Kwon
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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Soo-Young Lee
1Biotechnology Research Institute, Celltrion Inc., Incheon, Republic of Korea
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  • ORCID record for Soo-Young Lee
  • For correspondence: sooyoung.lee@celltrion.com
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Abstract

The Delta variant originally from India is rapidly spreading across the world and causes to resurge infections of SARS-CoV-2. We previously reported that CT-P59 presented its in vivo potency against Beta and Gamma variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on the Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal study. CT-P59 showed reduced antiviral activity but enabled neutralization against Delta, Epsilon, and Kappa variants in cells. In line with in vitro results, the mouse challenge experiment with the Delta variant substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against the Delta variant infection, hinting that CT-P59 has therapeutic potency for patients infected with Delta and its associated variants.

Highlights

  • CT-P59 exerts the antiviral effect on authentic Delta, Epsilon and Kappa variants in cell-based experiments.

  • CT-P59 showed neutralizing potency against variants including Delta, Epsilon, Kappa, L452R, T478K and P681H pseudovirus variants.

  • The administration of clinically relevant dose of CT-P59 showed in vivo

  • protection against Delta variants in animal challenge experiment.

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 July 23, 2021.
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The in vitro and in vivo potency of CT-P59 against Delta and its associated variants of SARS-CoV-2
Dong-Kyun Ryu, Hye-Min Woo, Bobin Kang, Hanmi Noh, Jong-In Kim, Ji-Min Seo, Cheolmin Kim, Minsoo Kim, Jun-Won Kim, Nayoung Kim, Pyeonghwa Jeon, Hansaem Lee, Jeong-Sun Yang, Kyung-Chang Kim, Joo-Yeon Lee, Min-Ho Lee, Sang-Seok Oh, Hyo-Young Chung, Ki-Sung Kwon, Soo-Young Lee
bioRxiv 2021.07.23.453472; doi: https://doi.org/10.1101/2021.07.23.453472
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The in vitro and in vivo potency of CT-P59 against Delta and its associated variants of SARS-CoV-2
Dong-Kyun Ryu, Hye-Min Woo, Bobin Kang, Hanmi Noh, Jong-In Kim, Ji-Min Seo, Cheolmin Kim, Minsoo Kim, Jun-Won Kim, Nayoung Kim, Pyeonghwa Jeon, Hansaem Lee, Jeong-Sun Yang, Kyung-Chang Kim, Joo-Yeon Lee, Min-Ho Lee, Sang-Seok Oh, Hyo-Young Chung, Ki-Sung Kwon, Soo-Young Lee
bioRxiv 2021.07.23.453472; doi: https://doi.org/10.1101/2021.07.23.453472

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