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：2004
卷号：101
期号：14
页码：5042-5047
DOI：10.1073/pnas.0401351101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Bacillus anthracis is surrounded by an antiphagocytic polypeptide capsule composed of poly {gamma}-D-glutamic acid ({gamma}DPGA). {gamma}DPGA has been identified recently as a potential target for vaccine development. Studies of the role of {gamma}DPGA in disease have been hampered by the poor Ab response to this antigen and the lack of immunochemical reagents. As a consequence, neither the extent of {gamma}DPGA production during anthrax nor the protective activity of {gamma}DPGA Abs in inhalation anthrax are known. Here we report production of IgG Abs to {gamma}DPGA in mice following an immunization regimen using {gamma}DPGA in combination with agonist mAbs to CD40. mAbs were produced that are specific for {gamma}DPGA. Passive immunization with {gamma}DPGA mAbs protected >90% of mice in a pulmonary model of anthrax that was lethal in control mice (P < 0.0001). Use of {gamma}DPGA mAb in an antigen detection immunoassay found that the appearance of {gamma}DPGA in serum coincided with the emergence of bacteremia. These studies identify CD40 stimulation as a means for production of Ab and generation of mAbs against a weakly immunogenic antigen and demonstrate that the capsule is an effective target for immunoprotection and for antigen detection in the diagnosis of anthrax.
