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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

Affinity and kinetic assay.hmPA6 affinity and kinetics assays showed five curves with different concentrations of anti-PA IgG ranging from 5 to 80 nmol/L; Kd = 1.438 × 10−10 M with PA83 at 25 μg/mL.
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f4: Affinity and kinetic assay.hmPA6 affinity and kinetics assays showed five curves with different concentrations of anti-PA IgG ranging from 5 to 80 nmol/L; Kd = 1.438 × 10−10 M with PA83 at 25 μg/mL.

Mentions: The equilibrium dissociation constant (Kd) for hmPA6 was determined by BiaCoreX100 analysis. The rate constants kon and koff were evaluated directly from the BiaCoreX100 sensogram. The Kd was also determined using the BiaCoreX100. One striking feature of hmPA6 is its very slow off rate, which may explain its high affinity of 1.438 × 10−10 M (Fig. 4).


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)

Affinity and kinetic assay.hmPA6 affinity and kinetics assays showed five curves with different concentrations of anti-PA IgG ranging from 5 to 80 nmol/L; Kd = 1.438 × 10−10 M with PA83 at 25 μg/mL.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Affinity and kinetic assay.hmPA6 affinity and kinetics assays showed five curves with different concentrations of anti-PA IgG ranging from 5 to 80 nmol/L; Kd = 1.438 × 10−10 M with PA83 at 25 μg/mL.
Mentions: The equilibrium dissociation constant (Kd) for hmPA6 was determined by BiaCoreX100 analysis. The rate constants kon and koff were evaluated directly from the BiaCoreX100 sensogram. The Kd was also determined using the BiaCoreX100. One striking feature of hmPA6 is its very slow off rate, which may explain its high affinity of 1.438 × 10−10 M (Fig. 4).

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