"The current objective is to develop a therapeutic superior to both MB-003 and ZMAb, which could be used for outbreak patients, primary health-care providers, as well as high-containment laboratory workers in the future... To extend the antibody half-life in humans and to facilitate clinical acceptance, the individual murine antibodies in ZMAb were first chimaerized with human constant regions (cZMAb; components: c1H3, c2G4 and c4G7). The cZMAb components were then produced in Nicotiana benthamiana, using the large-scale, Current Good Manufacturing Practice-compatible Rapid Antibody Manufacturing Platform (RAMP) and magnICON vectors that currently also manufactures the individual components of cocktail MB-003, before efficacy testing in animals."In Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp : Nature : Nature Publishing Group
Summary
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.
@ Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp : Nature : Nature Publishing Group:
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