Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp

• Published in: Nature (London) 2014-10, Vol.514 (7520), p.47-53
• Main Authors: Qiu, Xiangguo, Wong, Gary, Audet, Jonathan, Bello, Alexander, Fernando, Lisa, Alimonti, Judie B., Fausther-Bovendo, Hugues, Wei, Haiyan, Aviles, Jenna, Hiatt, Ernie, Johnson, Ashley, Morton, Josh, Swope, Kelsi, Bohorov, Ognian, Bohorova, Natasha, Goodman, Charles, Kim, Do, Pauly, Michael H., Velasco, Jesus, Pettitt, James, Olinger, Gene G., Whaley, Kevin, Xu, Bianli, Strong, James E., Zeitlin, Larry, Kobinger, Gary P.
• Format: Article
• Language: English
• Subjects: 13/1; 13/106; 13/31; 631/250/251; 631/326/22/1295; 631/326/596/2042; Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - therapeutic use; Antibodies, Viral - immunology; Antibodies, Viral - therapeutic use; Blood; Cross Reactions - immunology; Ebola virus; Ebola virus infections; Ebolavirus - immunology; Enzyme-Linked Immunosorbent Assay; Experiments; Female; Guinea; Guinea Pigs; Hemorrhagic Fever, Ebola - blood; Hemorrhagic Fever, Ebola - drug therapy; Hemorrhagic Fever, Ebola - immunology; Hemorrhagic Fever, Ebola - virology; Humanities and Social Sciences; Immunization, Passive; Infections; Macaca mulatta - immunology; Macaca mulatta - virology; Male; Medical research; Medicine, Experimental; Molecular Sequence Data; Monoclonal antibodies; multidisciplinary; Outbreaks; Physiological aspects; Science; Sequence Alignment; Studies; Vaccines; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - immunology; Viremia - drug therapy; Viremia - immunology; Viremia - virology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature13777

Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use. A new treatment, containing an optimized cocktail of three monoclonal antibodies against Ebola virus, provided full protection and disease reversal in rhesus monkeys when given under conditions in which controls succumbed by day 8; this new therapy may be a good candidate for treating Ebola virus infection in human patients. Immunotherapy in advanced Ebola virus disease This study shows that ZMapp, an optimized cocktail of three monoclonal antibodies that has been pressed into clinical use in response to the current Ebola virus disease epidemic, was able to rescue all of 18 rhesus macaques when treatment was initiated up to five days post-infection. All three controls had died by day eight.