Therapeutic efficacy of CT-P59 against P.1 variant of SARS-CoV-2
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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.
Highlights
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CT-P59 could bind to and neutralize P.1 variant, but CT-P59 showed reduced susceptibility in in vitro tests.
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The clinical dosage of CT-P59 demonstrated in vivo therapeutic potency against P.1 variants in hACE2-expressing mice challenge study.
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CT-P59 ameliorates their body weight loss and prevents the lethality in P.1 variant-infected mice.
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SciScore for 10.1101/2021.07.08.451696: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All procedures were approved by the Institutional Animal Care and Use Committee at the IVI (IACUC Approval No. 2020-021). 2.7. Sex as a biological variable Animal experiments: 8-week-old female human ACE2 transgenic mice, tg(K18-ACE2)2Prlmn, were purchased from The Jackson Laboratory (ME, USA). Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The cells were fixed and permeabilized, followed by treatment with a murine anti-nucleocapsid monoclonal antibody (Sino Biological), a secondary anti-mouse IgG peroxidase conjugate (Thermo Scientific) and TrueBlue (KPL) substrate. anti-nucleocap…SciScore for 10.1101/2021.07.08.451696: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All procedures were approved by the Institutional Animal Care and Use Committee at the IVI (IACUC Approval No. 2020-021). 2.7. Sex as a biological variable Animal experiments: 8-week-old female human ACE2 transgenic mice, tg(K18-ACE2)2Prlmn, were purchased from The Jackson Laboratory (ME, USA). Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The cells were fixed and permeabilized, followed by treatment with a murine anti-nucleocapsid monoclonal antibody (Sino Biological), a secondary anti-mouse IgG peroxidase conjugate (Thermo Scientific) and TrueBlue (KPL) substrate. anti-nucleocapsidsuggested: Noneanti-mouse IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Derivatives of HEK-293T cells expressing ACE2 were generated by transducing HEK-293T (ATCC, CRL-3216) cells with ACE2 (Addgene, #145839). HEK-293Tsuggested: ATCC Cat# CRL-3216, RRID:CVCL_0063)HEK293T-ACE2 cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% (v/v) HEK293T-ACE2suggested: NoneThe inocula infected ACE2-expressing HEK293T cells. HEK293Tsuggested: CCLV Cat# CCLV-RIE 1018, RRID:CVCL_0063)The lung samples and nasal washes were 4-fold serially diluted in DMEM and inoculated to Vero E6 cells in a 12-well plate. Vero E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Animal experiments: 8-week-old female human ACE2 transgenic mice, tg(K18-ACE2)2Prlmn, were purchased from The Jackson Laboratory (ME, USA). tg(K18-ACE2)2Prlmnsuggested: RRID:IMSR_JAX:035247)Software and Algorithms Sentences Resources After 72 h, luciferase activities were measured and IC50 values were calculated with Prism. 2.5. Microneutralization (ViroSpot) assay: To examine the susceptibility of SARS-CoV-2 variants, a microneutralization assay was performed as previously described [12]. Prismsuggested: (PRISM, RRID:SCR_005375)Images of all wells were acquired by a CTL Immunospot analyzer, equipped with Biospot® software to quantitate the nucleocapsid-positive cells. 2.6. Biospot®suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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