Title:Antibody Mixtures to treat Ebola
Volume: 6
Issue: 1
Author(s): T. Shantha Raju
Affiliation:
Keywords:
Ebola, filovirus, glycoprotein, antibody, IgG, antibody mixtures, glycosylation, transgenic, recombinant,
biotherapeutics.
Abstract: Background: Ebola virus (EBOV) is a single-stranded RNA filovirus and its genome consists of seven
genes. Among these seven genes, the glycoprotein (GP) gene encodes the only transmembrane protein
of EBOV which consists of disulfide linked glycoprotein 1 (GP1) and glycoprotein 2 (GP2). The two
glycoproteins i.e. GP1 and GP2 are furin-cleavage fragments of GP. Both GP1 and GP2 are heavily
glycosylated. The GP1 and GP2 heterodimers forms trimeric spikes and are critical for EBOV
attachment to host cells. The GP1 and GP2 are also involved in the catalysis of membrane fusion
following viral attachment. Hence both are key targets to develop therapeutics to combat the deadly
viral disease.
Methods: ZMapp is an antibody mixture consisting of three chimeric monoclonal antibodies against GP.
The three antibody components are called c13C6, c2G4, and c4G7 that were isolated from mice
immunized with a recombinant vesicular stomatitis virus (VSV) in which the VSV glycoprotein was
replaced with the GP from Ebola virus. The recombinant component antibodies of ZMapp were
produced using a plant expression system.
Results: During the recent Ebola outbreak, ZMapp was used to treat EBOV infection in a number of
patients in the USA and abroad on compassionate use basis under the expanded access program of US
FDA (United States Food and Drug Administration). Seven patients were treated with ZMapp and five
of the treated patients survived. Hence, ZMapp gained worldwide attention to treat Ebola.
Conclusions: ZMapp appears to be safe and effective treatment for Ebola. This article discusses the
biochemical characteristics of ZMapp in relation to the development of the antibody mixtures as
biotherapeutics and the efforts to produce ZMapp component antibodies in mammalian cells which
would increase the production yield and efficiency along with the possible decrease in cost of treatment.
