Development and characterization of two equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19
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‐Muñoz, Rónald Sánchez, José Marı́a Gutiérrez, Cecilia Díaz, Alberto Alape‐Girón
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.