期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 14, 页码 5042-5047出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0401351101
关键词
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资金
- NCI NIH HHS [R01 CA072669, CA-99572, CA-72669] Funding Source: Medline
- NIAID NIH HHS [R01 AI014209-27, R01 AI014209, R37 AI014209, R01 AI059348, AI-14209] Funding Source: Medline
Bacillus anthracis is surrounded by an antiphagocytic polypeptide capsule composed Of Poly gamma-D-glutamic acid (gammaDPGA). gammaDPGA has been identified recently as a potential target for vaccine development. Studies of the role of gammaDPGA 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 gammaDPGA production during anthrax nor the protective activity of gammaDPGA Abs in inhalation anthrax are known. Here we report production of IgG Abs to gammaDPGA in mice following an immunization regimen using gammaDPGA in combination with agonist mAbs to CD40. mAbs were produced that are specific for gammaDPGA. Passive immunization with gammaDPGA mAbs protected > 90% of mice in a pulmonary model of anthrax that was lethal in control mice (P < 0.0001). Use of gammaDPGA mAb in an antigen detection immunoassay found that the appearance of gammaDPGA 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.
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