title: A non-glycosylated, plant-produced human monoclonal antibody against anthrax protective antigen protects mice and non-human primates from B. anthracis spore challenge.
abstract: The health and economic burden of infectious diseases in general and bioterrorism in particular necessitate the development of medical countermeasures. One proven approach to reduce the disease burden and spread of pathogen is treatment with monoclonal antibodies (mAb). mAbs can prevent or reduce severity of the disease by variety of mechanisms, including neutralizing pathogen growth, limiting its spread from infected to adjacent cells, or by inhibiting biological activity of toxins, such as anthrax lethal toxin. Here, we report the production of glycosylated (pp-mAb (PA) ) and non-glycosylated (pp-mAb (PANG) ) versions of a plant-derived mAb directed against protective antigen (PA) of Bacillus anthracis in Nicotiana benthamiana plants using agroinfiltration. Both forms of the antibody were able to neutralize anthrax lethal toxin activity in vitro and protect mice against an intraperitoneal challenge with spores of B. anthracis Sterne strain. A single 180 µg intraperitoneal dose of pp-mAb (PA) or pp-mAb (PANG) provided 90% and 100% survival, respectively. When tested in non-human primates, pp-mAb (PANG) was demonstrated to be superior to pp-mAb (PA) in that it had a significantly longer terminal half-life and conferred 100% protection against a lethal dose of aerosolized anthrax spore challenge after a single 5 mg/kg intravenous dose compared to a 40% survival rate conferred by pp-mAb (PA) . This study demonstrates the potential of a plant-produced non-glycosylated antibody as a useful tool for the treatment of inhalation anthrax.
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, Newark, DE, USA.
authors.forename: Vadim
authors.initials: V
authors.lastname: Mett
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Chichester
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Stewart
authors.forename: Konstantin
authors.initials: K
authors.lastname: Musiychuk
authors.forename: Hong
authors.initials: H
authors.lastname: Bi
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Reifsnyder
authors.forename: Anna K
authors.initials: AK
authors.lastname: Hull
authors.forename: Mark T
authors.initials: MT
authors.lastname: Albrecht
authors.forename: Stanley
authors.initials: S
authors.lastname: Goldman
authors.forename: Les W J
authors.initials: LW
authors.lastname: Baillie
authors.forename: Vidadi
authors.initials: V
authors.lastname: Yusibov
mesh_terms: D000818:Animals; D000881:Anthrax / Q000628:therapy*; D000907:Antibodies, Bacterial / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D000942:Antigens, Bacterial; D000992:Antitoxins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D030821:Plants, Genetically Modified / Q000235:genetics; D018419:Primate Diseases / Q000628:therapy; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D012376:Rodent Diseases / Q000628:therapy; D016019:Survival Analysis; D014026:Nicotiana / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D011994:Recombinant Proteins; C030325:anthrax toxin