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

Xiong S, Tang Q, Liang X, Zhou T, Yang J, Liu P, Chen Y, Wang C, Feng Z, Zhu J - Sci Rep (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Western blot.M, molecular weight marker (NEB, USA); lane 1, lysates of rPA63 recombinant bacteria; lane 2, lysates of E. coli BL21.
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f2: Western blot.M, molecular weight marker (NEB, USA); lane 1, lysates of rPA63 recombinant bacteria; lane 2, lysates of E. coli BL21.

Mentions: Western blot analysis showed that hmPA6 could specifically recognize rPA63 (Fig. 2). No reaction was seen with the negative control.


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

Xiong S, Tang Q, Liang X, Zhou T, Yang J, Liu P, Chen Y, Wang C, Feng Z, Zhu J - Sci Rep (2015)

Western blot.M, molecular weight marker (NEB, USA); lane 1, lysates of rPA63 recombinant bacteria; lane 2, lysates of E. coli BL21.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488766&req=5

f2: Western blot.M, molecular weight marker (NEB, USA); lane 1, lysates of rPA63 recombinant bacteria; lane 2, lysates of E. coli BL21.
Mentions: Western blot analysis showed that hmPA6 could specifically recognize rPA63 (Fig. 2). No reaction was seen with the negative control.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus