the most advanced Ebola treatment is based on antibody-mediated therapy. In an
early attempt, remarkable expression levels (0.5 mg per gram of fresh tissue) of a
protective IgG against Ebola virus GP1, harnessing the geminivirus DNA replicon of
bean yellow dwarf virus, were reported (Huang et al. 2010). At that time, the multireplicon vector represented a significant advance in transient expression technology
for antibody production in plants.
As previously illustrated, Mapp Biopharmaceutical, Inc., is involved in a research
to find the best immunotherapy against Ebola, and the company has tested the drug
MB-003, a mAb cocktail consisting of three human and human-mouse chimeric
mAbs c13C6, h13F6 and c6D8 produced in CHO cells (Olinger Jr et al. 2012).
When produced from plants, MB-003 resulted three times as effective as CHO cellproduced recombinant counterpart mAbs, most likely due to the absence of core
fucose residues on the Fc region of the plant-derived mAbs, which results in
enhanced antibody-dependent cellular cytotoxicity (Zeitlin et al. 2011). Nowadays
the most advanced, optimized anti-Ebola mAb composition is the ZMapp cocktail,
consisting of selected components from MB-003 (c13C6) and ZMAb (humanized
c2G4 and c4G7) (Qiu et al. 2014). Using Magnifection, ZMapp was entirely
produced in the glycoengineered N. benthamiana line ΔXT/FT (Strasser et al.
2008) as a product of LeafBio (San Diego, California, USA), a joint venture of
Mapp Biopharmaceutical and Defyrus (Toronto, Canada) and was manufactured
under cGMP at the Kentucky BioProcessing facility.
Although ZMapp safety had not been previously evaluated in humans, during the
2014–2015 Ebola outbreak in West Africa, it was administered outside clinical trials
in compassionate use of experimental interventions to seven Ebola patients as a postexposure therapy. Of these patients, five significantly improved and recovered from
the disease even though the treatment was initiated at least 9 days after infection.
Nevertheless, a randomized phase I/II clinical trial of ZMapp as a putative
investigational therapeutic in the treatment of patients with known Ebola infection
is currently underway (ClinicalTrials.gov. 2015. Putative investigational therapeutics in the treatment of patients with known Ebola infection. Stud. Rec.
NCT02363322, Natl. Inst. Health, Bethesda, MD. https://clinicaltrials.gov/ct2/
show/NCT0236332237).
Today’s state of the art indicates ZMapp as an effective drug for Ebola patients;
however its supply is limited. Providing sufficient quantities of this biological is
challenging due to the high dosage required for optimal therapy (Qiu et al. 2014) and
to the limited capacity of the plant production system. Nevertheless, Mapp Biopharmaceutical has signed a contract with the US Department of Health and Human
Services with the aim to accelerate the drug’s development (McCarthy 2014).
Other plant biopharming companies are joining the global efforts against Ebola.
Medicago, (Quebec, Canada), in the framework of a task order from the Biomedical
Advanced Research and Development Authority at the US Department of Health
and Human Services, is producing three anti-Ebola virus monoclonal antibodies
(mAbs) with expected performance comparable to that of ZMapp™. In parallel, the
Fraunhofer USA Center for Molecular Biotechnology is producing these anti-EBOV
mAbs for the Biomedical Advanced Research and Development Authority, and
88
S. Massa et al.
early attempt, remarkable expression levels (0.5 mg per gram of fresh tissue) of a
protective IgG against Ebola virus GP1, harnessing the geminivirus DNA replicon of
bean yellow dwarf virus, were reported (Huang et al. 2010). At that time, the multireplicon vector represented a significant advance in transient expression technology
for antibody production in plants.
As previously illustrated, Mapp Biopharmaceutical, Inc., is involved in a research
to find the best immunotherapy against Ebola, and the company has tested the drug
MB-003, a mAb cocktail consisting of three human and human-mouse chimeric
mAbs c13C6, h13F6 and c6D8 produced in CHO cells (Olinger Jr et al. 2012).
When produced from plants, MB-003 resulted three times as effective as CHO cellproduced recombinant counterpart mAbs, most likely due to the absence of core
fucose residues on the Fc region of the plant-derived mAbs, which results in
enhanced antibody-dependent cellular cytotoxicity (Zeitlin et al. 2011). Nowadays
the most advanced, optimized anti-Ebola mAb composition is the ZMapp cocktail,
consisting of selected components from MB-003 (c13C6) and ZMAb (humanized
c2G4 and c4G7) (Qiu et al. 2014). Using Magnifection, ZMapp was entirely
produced in the glycoengineered N. benthamiana line ΔXT/FT (Strasser et al.
2008) as a product of LeafBio (San Diego, California, USA), a joint venture of
Mapp Biopharmaceutical and Defyrus (Toronto, Canada) and was manufactured
under cGMP at the Kentucky BioProcessing facility.
Although ZMapp safety had not been previously evaluated in humans, during the
2014–2015 Ebola outbreak in West Africa, it was administered outside clinical trials
in compassionate use of experimental interventions to seven Ebola patients as a postexposure therapy. Of these patients, five significantly improved and recovered from
the disease even though the treatment was initiated at least 9 days after infection.
Nevertheless, a randomized phase I/II clinical trial of ZMapp as a putative
investigational therapeutic in the treatment of patients with known Ebola infection
is currently underway (ClinicalTrials.gov. 2015. Putative investigational therapeutics in the treatment of patients with known Ebola infection. Stud. Rec.
NCT02363322, Natl. Inst. Health, Bethesda, MD. https://clinicaltrials.gov/ct2/
show/NCT0236332237).
Today’s state of the art indicates ZMapp as an effective drug for Ebola patients;
however its supply is limited. Providing sufficient quantities of this biological is
challenging due to the high dosage required for optimal therapy (Qiu et al. 2014) and
to the limited capacity of the plant production system. Nevertheless, Mapp Biopharmaceutical has signed a contract with the US Department of Health and Human
Services with the aim to accelerate the drug’s development (McCarthy 2014).
Other plant biopharming companies are joining the global efforts against Ebola.
Medicago, (Quebec, Canada), in the framework of a task order from the Biomedical
Advanced Research and Development Authority at the US Department of Health
and Human Services, is producing three anti-Ebola virus monoclonal antibodies
(mAbs) with expected performance comparable to that of ZMapp™. In parallel, the
Fraunhofer USA Center for Molecular Biotechnology is producing these anti-EBOV
mAbs for the Biomedical Advanced Research and Development Authority, and
88
S. Massa et al.