mAbs to Bacillus anthracis capsular antigen for immunoprotection in anthrax and detection of antigenemia
mAbs to Bacillus anthracis capsular antigen for immunoprotection in anthrax and detection of antigenemia
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DOI：
10.1073/pnas.0401351101
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发表时间：
2004-04-06
影响因子：
11.1
通讯作者：
Lyons, CR
中科院分区：
文献类型：
--
作者：
Kozel, TR;Murphy, WJ;Lyons, CR
炭疽芽孢杆菌被一种由聚γ - d -谷氨酸（gammaDPGA）组成的抗吞噬多肽胶囊包围。gammaDPGA最近被确定为疫苗开发的潜在靶点。关于gammaDPGA在疾病中的作用的研究一直受到抗体对该抗原的不良反应和缺乏免疫化学试剂的阻碍。因此，无论是炭疽期间γ madpga产生的程度，还是γ madpga抗体对吸入性炭疽的保护作用都不为人所知。在这里，我们报告了在使用gammaDPGA与CD40激动剂单克隆抗体联合免疫方案后，小鼠产生针对gammaDPGA的IgG抗体。产生了针对gammaDPGA的单克隆抗体。被动免疫gammaDPGA单克隆抗体对炭疽肺模型小鼠的保护率为90% （P < 0.0001）。在抗原检测免疫分析中使用gammaDPGA单抗发现血清中gammaDPGA的出现与菌血症的出现一致。这些研究确定CD40刺激是产生抗体和产生针对弱免疫原性抗原的单克隆抗体的一种手段，并证明该胶囊是免疫保护和炭疽诊断中抗原检测的有效靶标。
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.