In Vitro Characterization and In Vivo Effectiveness of Ebola Virus Specific Equine Polyclonal F(ab′)2

• Published in: The Journal of infectious diseases 2019-06, Vol.220 (1), p.41-45
• Main Authors: Racine, Trina, Denizot, Mélanie, Pannetier, Delphine, Nguyen, Ludovic, Pasquier, Anaïs, Raoul, Hervé, Saluzzo, Jean-François, Kobinger, Gary, Veas, Francisco, Herbreteau, Cécile H
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Ebola virus; Ebolavirus; Ebolavirus - immunology; Female; Hemorrhagic Fever, Ebola - immunology; Hemorrhagic Fever, Ebola - veterinary; Hemorrhagic Fever, Ebola - virology; Horses - immunology; Horses - virology; Immunization - methods; Immunoglobulin Fragments - immunology; Immunoglobulin G; Immunoglobulin G - immunology; Mice; Mice, Inbred BALB C; Nanoparticles; Trimers; Vaccination - methods
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiz068

Abstract There is no vaccine or approved therapy against lethal Ebola virus (EBOV). We investigated a proven technology platform to produce polyclonal IgG fragments, F(ab′)2, against EBOV. Horses immunized with nanoparticles harboring surface glycoprotein trimers of EBOV-Zaire/Makona produced anti-Ebola IgG polyclonal antibodies with high neutralization activity. Highly purified equine anti-Ebola F(ab′)2 showed strong cross-neutralization of 2 Zaire EBOV strains (Gabon 2001 and Makona) and in vivo 3 or 5 daily F(ab′)2 intraperitoneal injections provided 100% protection to BALB/c mice against lethal EBOV challenge. Rapid preparation of purified equine anti-Ebola F(ab′)2 offers a potentially efficient therapeutic approach against EBOV disease in humans. Applying techniques similar to the one used to produce other equine immunoglobulin fragments (ie, F(ab′)2 antirabies, anti-H5N1, or antivenoms) we prepared F(ab′)2 that neutralized Ebola viruses in vitro and protected BALB/c mice against lethal Ebola challenge in vivo.