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Development and pre-clinical characterization of two therapeutic equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19
bioRxiv - Microbiology Pub Date : 2020-10-19 , DOI: 10.1101/2020.10.17.343863
Guillermo León , María Herrera , Mariángela Vargas , Mauricio Arguedas , Andrés Sánchez , Álvaro Segura , Aarón Gómez , Gabriela Solano , Eugenia Corrales-Aguilar , Kenneth Risner , Aarthi Narayanan , Charles Bailey , Mauren Villalta , Andrés Hernández , Adriana Sánchez , Daniel Cordero , Daniela Solano , Gina Durán , Eduardo Segura , Maykel Cerdas , Deibid Umaña , Edwin Moscoso , Ricardo Estrada , Jairo Gutiérrez , Marcos Méndez , Ana Cecilia Castillo , Laura Sánchez , José María Gutiérrez , Cecilia Díaz , Alberto Alape

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.

中文翻译:

两种针对SARS-CoV-2蛋白的治疗性马制剂的开发和临床前表征,可用于COVID-19的潜在治疗

在当前因SARS-CoV-2爆发而引起的全球紧急情况下,被动免疫疗法已成为COVID-19的有前途的治疗方法。在动物衍生产品中,马类制剂仍是治疗因动物叮咬和st伤而引起的毒害的基石疗法。因此,我们利用数十年的蛇抗蛇毒素生产经验,开发并临床评估了两种抗SARS-CoV-2多克隆马制剂,作为COVID-19的潜在替代疗法。我们用S1(抗S1)或S1,N和SEM镶嵌(抗Mix)病毒重组蛋白的混合物免疫了两组马。初免后7周,马匹达到最大抗病毒抗体水平,并且没有出现严重的急性或慢性不良临床改变。通过用辛酸的超免疫血浆沉淀制备了两种全IgG制剂,然后配制用于肠胃外使用。两种制剂的理化和微生物学质量均相似,并显示出针对S1蛋白和受体结合域(RBD)的ELISA免疫反应性。该抗-Mix制剂还表现出针对N蛋白的免疫反应性。由于高抗S1和抗RBD抗体含量,最终产品具有很高的SARS-CoV-2感染的体外中和能力,比人类恢复性血浆库高80倍。两种产品的临床前质量概况相似,但是必须在临床试验中测试临床疗效和安全性。我们在此描述的技术策略可以被其他生产者采用,特别是在中低收入国家。
更新日期:2020-10-20
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