title: 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.affiliation: 1] Department of Pathology, Nanjing Medical University, Nanjing 210029, China [2] Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Siping
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tang
authors.affiliation: National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206 China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Huadong Medical Institute of Biotechniques, Nanjing 210002, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Huadong Medical Institute of Biotechniques, Nanjing 210002, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: 1] Department of Pathology, Nanjing Medical University, Nanjing 210029, China [2] Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Huadong Medical Institute of Biotechniques, Nanjing 210002, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1] Department of Pathology, Nanjing Medical University, Nanjing 210029, China [2] Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Feng
authors.affiliation: 1] Huadong Medical Institute of Biotechniques, Nanjing 210002, China [2] Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000881:Anthrax / Q000188:drug therapy*; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D001408:Bacillus anthracis / Q000276:immunology; D001427:Bacterial Toxins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011916:Rats, Inbred F344; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D011993:Recombinant Fusion Proteins; C030325:anthrax toxin