In Vitro Characterization and In Vivo Effectiveness of Ebola Virus Specific Equine Polyclonal F(ab’)2.
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.
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Publication Date: 2019-03-11 PubMed ID: 30852585DOI: 10.1093/infdis/jiz068Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article discusses the development and testing of a therapeutic approach against the Ebola virus, using equine-produced, anti-Ebola polyclonal antibodies. The approach was found to provide 100% protection in treated mice against a lethal Ebola virus challenge.
Research Purpose and Methodology
- The research was conducted to explore a novel therapeutic strategy for combating Ebola virus disease, a severe illness with high mortality rates and no currently approved vaccine or treatment.
- The scientists utilized a well-established platform for generating F(ab’)2, which are antibody fragments derived from a process that cleaves a full antibody into two antigen-binding fragments and a crystallizable fragment. These F(ab’)2 fragments were generated from polyclonal antibodies, multiple antibodies that target different parts of an antigen, from immunized horses.
- The horses were immunized with nanoparticles embedding surface glycoprotein trimers of the Ebola virus (EBOV) strain Zaire/Makona, which led to the production of anti-Ebola IgG polyclonal antibodies.
- The neutralizing activity of these antibodies was assessed. They were then purified to obtain high concentrations of the equine anti-Ebola F(ab’)2.
Results and Findings
- The anti-Ebola IgG polyclonal antibodies produced by the horses were found to have strong neutralizing activity against the EBOV.
- The purified equine anti-Ebola F(ab’)2 demonstrated potent cross-neutralization for two different strains of Zaire EBOV, specifically the Gabon 2001 and Makona strains.
- In vivo tests involved administering 3 or 5 daily F(ab’)2 injections to BALB/c mice, a common model organism in research. These injections demonstrated a 100% protection rate against lethal Ebola virus challenges, indicating a high efficacy of the therapeutic approach.
Conclusion and Implications
- The study concluded that the generation of purified equine anti-Ebola F(ab’)2 through the immunization of horses presents a potentially effective method for controlling EBOV disease in humans.
- By leveraging the robust immune response of horses to EBOV, a highly effective therapeutic antibody can be rapidly prepared and potentially deployed for use in an Ebola virus outbreak scenario.
- This research not only contributes to the development of Ebola-specific therapies but could also provide insights into the use of similar methods for other viral diseases.
Cite This Article
APA
Racine T, Denizot M, Pannetier D, Nguyen L, Pasquier A, Raoul H, Saluzzo JF, Kobinger G, Veas F, Herbreteau CH.
(2019).
In Vitro Characterization and In Vivo Effectiveness of Ebola Virus Specific Equine Polyclonal F(ab’)2.
J Infect Dis, 220(1), 41-45.
https://doi.org/10.1093/infdis/jiz068 Publication
Researcher Affiliations
- Special Pathogens Program, National Microbiology Laboratory, Winnipeg, Canada.
- Department of Medical Microbiology, Winnipeg, Canada.
- Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Université Laval, Canada.
- Fab'entech, Lyon, France.
- INSERM, Jean Mérieux BSL-4 Laboratory, Lyon, France.
- Fab'entech, Lyon, France.
- Fab'entech, Lyon, France.
- INSERM, Jean Mérieux BSL-4 Laboratory, Lyon, France.
- Fab'entech, Lyon, France.
- Department of Medical Microbiology, Winnipeg, Canada.
- Department of Immunology, University of Manitoba, Winnipeg, Canada.
- Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Université Laval, Canada.
- Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia.
- Institut de Recherche pour le Développement, UMR-Ministère de la Défense, Faculté de Pharmacie, Université de Montpellier, France.
- Fab'entech, Lyon, France.
MeSH Terms
- Animals
- Antibodies, Neutralizing / immunology
- Antibodies, Viral / immunology
- 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 / immunology
- Mice
- Mice, Inbred BALB C
- Vaccination / methods
Citations
This article has been cited 4 times.- Li E, Han Q, Bi J, Wei S, Wang S, Zhang Y, Liu J, Feng N, Wang T, Wu J, Yang S, Zhao Y, Liu B, Yan F, Xia X. Therapeutic equine hyperimmune antibodies with high and broad-spectrum neutralizing activity protect rodents against SARS-CoV-2 infection. Front Immunol 2023;14:1066730.
- Andrade SA, Batalha-Carvalho JV, Curi R, Wen FH, Covas DT, Chudzinski-Tavassi AM, Moro AM. Equine Anti-SARS-CoV-2 Serum (ECIG) Binds to Mutated RBDs and N Proteins of Variants of Concern and Inhibits the Binding of RBDs to ACE-2 Receptor. Front Immunol 2022;13:871874.
- da Costa CBP, Martins FJ, da Cunha LER, Ratcliffe NA, Cisne de Paula R, Castro HC. COVID-19 and Hyperimmune sera: A feasible plan B to fight against coronavirus. Int Immunopharmacol 2021 Jan;90:107220.
- Martinez EJ, Chang WC, Chen WH, Hajduczki A, Thomas PV, Jensen JL, Choe M, Sankhala RS, Peterson CE, Rees PA, Kimner J, Soman S, Kuklis C, Mendez-Rivera L, Dussupt V, King J, Corbett C, Mayer SV, Fernandes A, Murzello K, Cookenham T, Hvizdos J, Kummer L, Hart T, Lanzer K, Gambacurta J, Reagan M, Duso D, Vasan S, Collins ND, Michael NL, Krebs SJ, Gromowski GD, Modjarrad K, Kaundinya J, Joyce MG. SARS-CoV-2 ferritin nanoparticle vaccines produce hyperimmune equine sera with broad sarbecovirus activity. iScience 2024 Oct 18;27(10):110624.
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