期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2011
卷号：108
期号：2
页码：739-744
DOI：10.1073/pnas.1017677108
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：One of the two essential virulence factors of Bacillus anthracis is the poly-{gamma}-D-glutamic acid ({gamma}DPGA) capsule. Five {gamma}DPGA-specific antibody antigen-binding fragments (Fabs) were generated from immunized chimpanzees. The two selected for further study, Fabs 11D and 4C, were both converted into full-length IgG1 and IgG3 mAbs having human IgG1 or IgG3 constant regions. These two mAbs had similar binding affinities, in vitro opsonophagocytic activities, and in vivo efficacies, with the IgG1 and IgG3 subclasses reacting similarly. The mAbs bound to {gamma}DPGA specifically with estimated binding affinities (Kd) of 35-70 nM and effective affinities (effective Kd) of 0.1-0.3 nM. The LD50 in an opsonophagocytic bactericidal assay was {approx}10 ng/mL of 11D or 4C. A single 30-{micro}g dose of either mAb given to BALB/c mice 18 h before challenge conferred about 50% protection against a lethal intratracheal spore challenge by the virulent B. anthracis Ames strain. More importantly, either mAb given 8 h or 20 h after challenge provided significant protection against lethal infection. Thus, these anti-{gamma}DPGA mAbs should be useful, alone or in combination with antitoxin mAbs, for achieving a safe and efficacious postexposure therapy for anthrax.
