Protective Effects of STI-2020 Antibody Delivered Post-Infection by the Intranasal or Intravenous Route in a Syrian Golden Hamster COVID-19 Model
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Abstract
We have previously reported that the SARS-CoV-2 neutralizing antibody, STI-2020, potently inhibits cytopathic effects of infection by genetically diverse clinical SARS-CoV-2 pandemic isolates in vitro, and has demonstrated efficacy in a hamster model of COVID-19 when administered by the intravenous route immediately following infection. We now have extended our in vivo studies of STI-2020 to include disease treatment efficacy, profiling of biodistribution of STI-2020 in mice when antibody is delivered intranasally (IN) or intravenously (IV), as well as pharmacokinetics in mice following IN antibody administration. Importantly, SARS-CoV-2-infected hamsters were treated with STI-2020 using these routes, and treatment effects on severity and duration of COVID-19-like disease in this model were evaluated. In SARS-CoV-2 infected hamsters, treatment with STI-2020 12 hours post-infection using the IN route led to a decrease in severity of clinical disease signs and a more robust recovery during 9 days of infection as compared to animals treated with an isotype control antibody. Treatment via the IV route using the same dose and timing regimen resulted in a decrease in the average number of consecutive days that infected animals experienced weight loss, shortening the duration of disease and allowing recovery to begin more rapidly in STI-2020 treated animals. Following IN administration in mice, STI-2020 was detected within 10 minutes in both lung tissue and lung lavage. The half-life of STI-2020 in lung tissue is approximately 25 hours. We are currently investigating the minimum effective dose of IN-delivered STI-2020 in the hamster model as well as establishing the relative benefit of delivering neutralizing antibodies by both IV and IN routes.
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SciScore for 10.1101/2020.10.28.359836: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: This study was reviewed and accepted by the animal study review committee (SRC) and conducted in accordance with IACUC guidelines. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Hamster challenge experiments: Female Syrian golden hamsters were obtained from Charles River Laboratories at 6 weeks of age. Table 2: Resources
Antibodies Sentences Resources Multi-Array 96-well plates (cat# L15XA-3, Meso Scale Discovery (MSD)) were coated with mouse anti-human IgG antibody (CH2 domain, cat# MA5-16929, ThermoFisher Scientific) at 2 μg/mL in 1X PBS (50μL/well), sealed, and incubated overnight at 4°C. anti-human IgGsug…SciScore for 10.1101/2020.10.28.359836: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: This study was reviewed and accepted by the animal study review committee (SRC) and conducted in accordance with IACUC guidelines. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Hamster challenge experiments: Female Syrian golden hamsters were obtained from Charles River Laboratories at 6 weeks of age. Table 2: Resources
Antibodies Sentences Resources Multi-Array 96-well plates (cat# L15XA-3, Meso Scale Discovery (MSD)) were coated with mouse anti-human IgG antibody (CH2 domain, cat# MA5-16929, ThermoFisher Scientific) at 2 μg/mL in 1X PBS (50μL/well), sealed, and incubated overnight at 4°C. anti-human IgGsuggested: (Thermo Fisher Scientific Cat# MA5-16929, RRID:AB_2538406)Plates were then washed 3X with 1X washing solution and 50 μL of Sulfo-Tag anti-human/NHP IgG antibody (cat no# D20JL-6, lot no# W0019029S, MSD), at 1/1,000 dilution in Blocker™ Casein in PBS was added to each well and plates were then incubated for 1-1.5 hours at room temperature on an orbital shaker. anti-human/NHP IgGsuggested: NoneAntibody treatments were administered IV with monoclonal antibodies (mAbs) against SARS-CoV-2 Spike, or isotype control mAb in up to 350 μL of formulation buffer to anesthetized animals at 12 hours-post inoculation. SARS-CoV-2suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Pharmacokinetic Study: Female CD-1-IGS (strain code #022) were obtained from Charles River Laboratories at 6-8 weeks of age. CD-1-IGSsuggested: NoneSoftware and Algorithms Sentences Resources Pharmacokinetic analysis of the collected ELISA data was performed with the Phoenix WiNnonlin suite of software (version 6.4, Certara) using a non-compartmental approach consistent with an IN bolus route of administration. Phoenixsuggested: (Phoenix, RRID:SCR_003163)Results 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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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.
- No funding statement was detected.
- No protocol registration statement was detected.
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