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ZMapp is an experimental biopharmaceutical drug comprising three chimeric monoclonal antibodies under development as a treatment for Ebola virus disease. The drug was first tested in humans during the 2014 West Africa Ebola virus outbreak, but has not been subjected to a randomized controlled trial to determine whether it works, and whether it is safe enough to allow on the market.

ZMapp is under development as a treatment for Ebola virus disease.[2] It was first used experimentally to treat some people with Ebola virus disease during the 2014 West African Ebola outbreak, but as of August 2014 it had not yet been tested in a clinical trial to support widespread usage in humans; it is not known whether it is effective to treat the disease, nor if it is safe.[3][4][5]

Like intravenous immunoglobulin therapy, ZMapp contains neutralizing antibodies[6] that provide passive immunity to the virus by directly and specifically reacting with it in a "lock and key" fashion.[7]

The drug is composed of three monoclonal antibodies (mAbs) that have been chimerized by genetic engineering.[8] The components are chimeric monoclonal antibody c13C6 from a previously existing antibody cocktail called "MB-003" and two chimeric mAbs from a different antibody cocktail called ZMab, c2G4 and c4G7.[2]

ZMapp is manufactured in the tobacco plant Nicotiana benthamiana in the bioproduction process known as "pharming" by Kentucky BioProcessing, a subsidiary of Reynolds American.[1][9][10]

The composite drug is being developed by Leaf Biopharmaceutical (LeafBio, Inc.), a San Diego based arm of Mapp Biopharmaceutical.[11] LeafBio created ZMapp in collaboration with its parent and Defyrus Inc., each of which had developed its own cocktail of antibodies, called MB-003 and ZMab.

MB-003 is a cocktail of three humanized or humanmouse chimeric mAbs: c13C6, h13F6 and c6D8.[2] A study published in September 2012 found that rhesus macaques infected with Ebola virus (EBOV) survived when receiving MB-003 (mixture of 3 chimeric monoclonal antibodies) one hour after infection. When treated 24 or 48 hours after infection, four of six animals survived and had little to no viremia and few, if any, clinical symptoms.[12]

MB-003 was created by Mapp Biopharmaceutical, based in San Diego, with years of funding from US government agencies including the National Institute of Allergy and Infectious Disease, Biomedical Advanced Research and Development Authority, and the Defense Threat Reduction Agency.[1][13]

ZMAb is a mixture of three mouse mAbs: m1H3, m2G4 and m4G7.[2] A study published in November 2013 found that EBOV-infected macaque monkeys survived after being given a therapy with a combination of three EBOV surface glycoprotein (EBOV-GP)-specific monoclonal antibodies (ZMAb) within 24 hours of infection. The authors concluded that post-exposure treatment resulted in a robust immune response, with good protection for up to 10 weeks and some protection at 13 weeks.[14]

ZMab was created by Defyrus, a Toronto-based biodefense company, funded by the Public Health Agency of Canada.[15] The identification of the optimal components from MB-003 and ZMab was carried out at the Public Health Agency of Canadas National Microbiology Laboratory in Winnipeg.[16]

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ZMapp - Wikipedia, the free encyclopedia