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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Autores: León Montero, Guillermo, Herrera Vega, María, Vargas Arroyo, Mariángela, Arguedas Gómez, Mauricio, Sánchez Brenes, Andrés, Segura Ruíz, Álvaro, Gómez Argüello, Aarón, Solano Blanco, María Gabriela, Corrales Aguilar, Eugenia, Risner, Kenneth, Narayanan, Aarthi, Bailey, Charles, Villalta Arrieta, Mauren, Hernández Bolaños, Andrés, Sánchez Sánchez,, Adriana, Cordero, Daniel, Solano Cneteno, Daniela, Durán Blanco, Gina, Segura Agüero, Eduardo, Cerdas Solís, Maykel, Umaña Blanco, Deibid, Moscoso Suárez, Edwin, Estrada Umaña, Ricardo, Gutiérrez González, Jairo, Méndez Alvarado, Marcos, Castillo Mora, Ana Cecilia, Sánchez Céspedes, Laura, Gutiérrez, José María, Díaz Oreiro, Cecilia, Alape Girón, Alberto
Formato: artículo original
Fecha de Publicación:2020
Descripción: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.
País:Kérwá
Institución:Universidad de Costa Rica
Repositorio:Kérwá
Lenguaje:Inglés
OAI Identifier:oai:kerwa.ucr.ac.cr:10669/103061
Acceso en línea:https://hdl.handle.net/10669/103061
https://doi.org/10.1101/2020.10.17.343863
Palabra clave:Coronavirus (SARS-CoV-2)
Coronavirus disease 2019 (COVID-19)
Experimental therapy
Viral proteins
Medical treatment
Immunology

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