Ebola GP-Specific Monoclonal Antibodies Protect Mice and Guinea Pigs from Lethal Ebola Virus Infection
Open Access
- 20 March 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Neglected Tropical Diseases
- Vol. 6 (3) , e1575
- https://doi.org/10.1371/journal.pntd.0001575
Abstract
Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as pools of 3–4 MAbs to test their protection against a lethal challenge with mouse- or guinea pig-adapted EBOV. Each of the 8 MAbs (100 µg) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven MAbs were effective 2 days post-infection (dpi), with 1 MAb demonstrating partial protection 3 dpi. In the guinea pigs each MAb showed partial protection at 1 dpi, however the mean time to death was significantly prolonged compared to the control group. Moreover, treatment with pools of 3–4 MAbs completely protected the majority of animals, while administration at 2–3 dpi achieved 50–100% protection. This data suggests that the MAbs generated are capable of protecting both animal species against lethal Ebola virus challenge. These results indicate that MAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection. Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against the Ebola virus surface glycoprotein, in mice and guinea pigs. Various combinations and doses of the neutralizing and non-neutralizing MAbs were tested, and a post-exposure treatment protocol was determined. There was 100% survival when guinea pigs received a mix of 3 neutralizing MAbs two days after a challenge with 1,000 LD50 of guinea pig-adapted EBOV. This data suggests that the MAbs generated are effective as a post-exposure therapeutic for a lethal Ebola virus infection. Development of a post-exposure therapeutic for an Ebola virus infection is vital due to the high lethality of the disease, the relative speed in which it kills, and the fact that no vaccine has been approved for human use. Additionally, is it unlikely that preventative vaccines will be employed, because Ebola virus infections occur primarily in Africa, and to date have only killed approximately 2,300 people making it financially unfeasible for a mass vaccination. Therefore, having an effective therapy in the event of an outbreak would be extremely beneficial.Keywords
This publication has 42 references indexed in Scilit:
- Functional Genomics Reveals the Induction of Inflammatory Response and Metalloproteinase Gene Expression during Lethal Ebola Virus InfectionJournal of Virology, 2011
- Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanismsVirology, 2010
- Mucosal Immunization of Cynomolgus Macaques with the VSVΔG/ZEBOVGP Vaccine Stimulates Strong Ebola GP-Specific Immune ResponsesPLOS ONE, 2009
- Newly Discovered Ebola Virus Associated with Hemorrhagic Fever Outbreak in UgandaPLoS Pathogens, 2008
- Recombinant Human Activated Protein C for the Postexposure Treatment of Ebola Hemorrhagic FeverThe Journal of Infectious Diseases, 2007
- The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic feverGenome Biology, 2007
- Neutralizing Antibody Fails to Impact the Course of Ebola Virus Infection in MonkeysPLoS Pathogens, 2007
- Effective Post-Exposure Treatment of Ebola InfectionPLoS Pathogens, 2007
- Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino OligomersPLoS Pathogens, 2006
- Studies of Ebola Virus Glycoprotein-Mediated Entry and Fusion by Using Pseudotyped Human Immunodeficiency Virus Type 1 Virions: Involvement of Cytoskeletal Proteins and Enhancement by Tumor Necrosis Factor AlphaJournal of Virology, 2005