A Novel Chimeric Anti-PA Neutralizing Antibody for Postexposure Prophylaxis and Treatment of Anthrax.

Abstract

Anthrax is a highly lethal infectious disease caused by the bacterium Bacillus anthracis, and the associated shock is closely related to the lethal toxin (LeTx) produced by the bacterium. The central role played by the 63 kDa protective antigen (PA63) region of LeTx in the pathophysiology of anthrax makes it an excellent therapeutic target. In the present study, a human/murine chimeric IgG mAb, hmPA6, was developed by inserting murine antibody variable regions into human constant regions using antibody engineering technology. hmPA6 expressed in 293F cells could neutralize LeTx both in vitro and in vivo. At a dose of 0.3 mg/kg, it could protect all tested rats from a lethal dose of LeTx. Even administration of 0.6 mg/kg hmPA6 48 h before LeTx challenge protected all tested rats. The results indicate that hmPA6 is a potential candidate for clinical application in anthrax treatment.

• Authors: Siping Xiong, Qi Tang, Xudong Liang, Tingting Zhou, Jin Yang, Peng Liu, Ya Chen, Changjun Wang, Zhenqing Feng, Jin Zhu
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 11776 (Jul 02 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26134518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Antigens, Bacterial
• Bacterial Toxins
• Recombinant Fusion Proteins
• anthrax toxin

Topics

• Amino Acid Sequence
• Animals
• Anthrax (drug therapy)
• Antibodies, Neutralizing (chemistry, pharmacology)
• Antigens, Bacterial (chemistry, immunology, pharmacology)
• Bacillus anthracis (immunology)
• Bacterial Toxins (chemistry, immunology, pharmacology)
• Cell Line
• Female
• Humans
• Molecular Sequence Data
• Protein Binding
• Rats, Inbred F344
• Recombinant Fusion Proteins (chemistry, pharmacology)