Recombinant Anthrax Toxin Receptor-Fc Fusion Proteins Produced in Plants Protect Rabbits Against Inhalational Anthrax.
|Title||Recombinant Anthrax Toxin Receptor-Fc Fusion Proteins Produced in Plants Protect Rabbits Against Inhalational Anthrax.|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Wycoff, KL, Belle A, Deppe D, Schaefer L, Maclean JM, Neuss S, Trilling AK, Liu S, Leppla SH, Geren IN, Pawlik J, Peterson JW|
|Journal||Antimicrobial agents and chemotherapy|
|Date Published||2010 Oct 18|
Inhalational anthrax, a zoonotic disease caused by inhalation of Bacillus anthracis spores, has a ∼50% fatality rate even when treated with antibiotics. Pathogenesis is dependent on the activity of two toxic noncovalent complexes - Edema toxin (EdTx) and Lethal toxin (LeTx). An essential component of both complexes, protective antigen (PA) binds with high affinity to the major receptor mediating lethality of anthrax toxin in vivo, capillary morphogenesis protein-2 (CMG2). Certain antibodies against PA have been shown to protect against anthrax in vivo. As an alternative to anti-PA antibodies, we produced a fusion of the extracellular domain of human CMG2 and human IgG Fc, using both transient and stable tobacco plant expression systems. Optimized expression led to the CMG2-Fc fusion protein being produced at high levels: 730 mg/kg fresh leaf weight in Nicotiana benthamiana and 65 mg/kg in N. tabacum. CMG2-Fc, purified from tobacco plants, fully protected rabbits against a lethal challenge with B. anthracis spores at a dose of 2 mg/kg body weight administered at the time of challenge. Treatment with CMG2-Fc did not interfere with development of the animals' own immunity to anthrax, as treated animals that survived an initial challenge also survived a re-challenge 30 days later. Glycosylation of the Fc (or lack thereof) had no significant effect on the protective potency of CMG2-Fc in rabbits or on its serum half-life, which was about 5 days. Significantly, CMG2-Fc effectively neutralized, in vitro, LeTx containing mutant forms of PA that were not neutralized by anti-PA monoclonal antibodies.
|Short Title||Antimicrob Agents Chemother|