title: Recombinant HSA-CMG2 Is a Promising Anthrax Toxin Inhibitor.
abstract: Anthrax toxin is the major virulence factor produced by Bacillus anthracis. Protective antigen (PA) is the key component of the toxin and has been confirmed as the main target for the development of toxin inhibitors. The inhibition of the binding of PA to its receptor, capillary morphogenesis protein-2 (CMG2), can effectively block anthrax intoxication. The recombinant, soluble von Willebrand factor type A (vWA) domain of CMG2 (sCMG2) has demonstrated potency against anthrax toxin. However, the short half-life of sCMG2 in vivo is a disadvantage for its development as a new anthrax drug. In the present study, we report that HSA-CMG2, a protein combining human serum albumin (HSA) and sCMG2, produced in the Pichia pastoris expression system prolonged the half-life of sCMG2 while maintaining PA binding ability. The IC50 of HSA-CMG2 is similar to those of sCMG2 and CMG2-Fc in in vitro toxin neutralization assays, and HSA-CMG2 completely protects rats from lethal doses of anthrax toxin challenge; these same challenge doses exceed sCMG2 at a sub-equivalent dose ratio and overwhelm CMG2-Fc. Our results suggest that HSA-CMG2 is a promising inhibitor of anthrax toxin and may contribute to the development of novel anthrax drugs.
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. byebyelll@163.com.|Center for Disease Control and Prevention of Navy, Beijing 101113, China. byebyelll@163.com.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. jackyguo@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. 18701522421@163.com.
authors.forename: Ju
authors.initials: J
authors.lastname: Liu
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. justforhere@126.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. yinying1028@sina.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. akta100@sina.com.
authors.forename: Dayong
authors.initials: D
authors.lastname: Dong
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. fuling3436@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Fu
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. xujunjie@sina.com.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China. cw0226@foxmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000633:toxicity*; D001427:Bacterial Toxins / Q000235:genetics / Q000633:toxicity*; D002460:Cell Line; D004926:Escherichia coli / Q000235:genetics; D008297:Male; D051379:Mice; D010957:Plasmids; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D018000:Receptors, Peptide / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D012709:Serum Albumin / Q000235:genetics / Q000494:pharmacology*
chemical_list: C447150:ANTXR2 protein, human; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; C030325:anthrax toxin
keywords: Bacillus anthracis; CMG2; HSA; anthrax toxin inhibitor; protective antigen