Development and pre-clinical characterization of two therapeutic equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19
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Abstract
In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited high in vitro neutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.
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SciScore for 10.1101/2020.10.17.343863: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: 2.1 Ethical Statement: All procedures involving animals in this study were approved by the Institutional Committee for the Care and Use of Laboratory Animals (CICUA) of the University of Costa Rica (Act 200-2020), and meet both ARRIVE Guidelines29 and International Guiding Principles for Biomedical Research Involving Animals30.
IACUC: COVID-19 convalescent human plasma collection and use was approved by the Central Committee of Pharmacotherapy (Act GM- CCF-1854-2020) ant the Institutional Bioethics Committee of the Caja Costarricense de Seguro Social (C.C.S.S.; Costa Rican Social Security Fund).
Consent: All donors were over 18 years old and provided an …SciScore for 10.1101/2020.10.17.343863: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: 2.1 Ethical Statement: All procedures involving animals in this study were approved by the Institutional Committee for the Care and Use of Laboratory Animals (CICUA) of the University of Costa Rica (Act 200-2020), and meet both ARRIVE Guidelines29 and International Guiding Principles for Biomedical Research Involving Animals30.
IACUC: COVID-19 convalescent human plasma collection and use was approved by the Central Committee of Pharmacotherapy (Act GM- CCF-1854-2020) ant the Institutional Bioethics Committee of the Caja Costarricense de Seguro Social (C.C.S.S.; Costa Rican Social Security Fund).
Consent: All donors were over 18 years old and provided an informed consent approved by the Institutional Committee of Health Record of the C.C.S.S. 2.2 Virus proteins: SARS-CoV-2 Spike S1 protein (code REC31828), SARS-CoV-2 Nucleocapsid protein (code REC31812), and SARS-CoV-2 Spike E-M mosaic protein (code REC31829) were purchased from The Native Antigen Company (Oxford, United Kingdom).Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
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.
- 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.
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