Recombinant anthrax toxin receptor-Fc fusion proteins produced in plants protect rabbits against inhalational anthrax

Keith L. Wycoff, Archana Belle, Dorothée Deppe, Leah Schaefer, James M. MacLean, Simone Haase, Anke K. Trilling, Shihui Liu, Stephen H. Leppla, Isin N. Geren, Jennifer Pawlik, Johnny Peterson

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Inhalational anthrax, a zoonotic disease caused by the 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). Protective antigen (PA), an essential component of both complexes, binds with high affinity to the major receptor mediating the 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 the development of the animals' own immunity to anthrax, as treated animals that survived an initial challenge also survived a rechallenge 30 days later. The 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.

Original languageEnglish (US)
Pages (from-to)132-139
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume55
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Anthrax
Morphogenesis
Rabbits
Antigens
Proteins
Tobacco
Bacillus anthracis
Spores
anthrax toxin receptors
Antibodies
Poisons
Zoonoses
Glycosylation
Inhalation
Half-Life
Immunity
Edema
Immunoglobulin G
Monoclonal Antibodies
Body Weight

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Recombinant anthrax toxin receptor-Fc fusion proteins produced in plants protect rabbits against inhalational anthrax. / Wycoff, Keith L.; Belle, Archana; Deppe, Dorothée; Schaefer, Leah; MacLean, James M.; Haase, Simone; Trilling, Anke K.; Liu, Shihui; Leppla, Stephen H.; Geren, Isin N.; Pawlik, Jennifer; Peterson, Johnny.

In: Antimicrobial Agents and Chemotherapy, Vol. 55, No. 1, 01.2011, p. 132-139.

Research output: Contribution to journalArticle

Wycoff, KL, Belle, A, Deppe, D, Schaefer, L, MacLean, JM, Haase, S, Trilling, AK, Liu, S, Leppla, SH, Geren, IN, Pawlik, J & Peterson, J 2011, 'Recombinant anthrax toxin receptor-Fc fusion proteins produced in plants protect rabbits against inhalational anthrax', Antimicrobial Agents and Chemotherapy, vol. 55, no. 1, pp. 132-139. https://doi.org/10.1128/AAC.00592-10
Wycoff, Keith L. ; Belle, Archana ; Deppe, Dorothée ; Schaefer, Leah ; MacLean, James M. ; Haase, Simone ; Trilling, Anke K. ; Liu, Shihui ; Leppla, Stephen H. ; Geren, Isin N. ; Pawlik, Jennifer ; Peterson, Johnny. / Recombinant anthrax toxin receptor-Fc fusion proteins produced in plants protect rabbits against inhalational anthrax. In: Antimicrobial Agents and Chemotherapy. 2011 ; Vol. 55, No. 1. pp. 132-139.
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