Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
Toxins (Basel). 2011 Aug;3(8):979-90. doi: 10.3390/toxins3080979. Epub 2011 Aug 9.
The primary immunogenic component of the currently approved anthrax vaccine is the protective antigen (PA) unit of the binary toxin system. PA-specific antibodies neutralize anthrax toxins and protect against infection. Recent research has determined that in humans, only antibodies specific for particular determinants are capable of effecting toxin neutralization, and that the neutralizing epitopes recognized by these antibodies are distributed throughout the PA monomer. The mechanisms by which the majority of these epitopes effect neutralization remain unknown. In this report we investigate the process by which a human monoclonal antibody specific for the amino-terminal domain of PA neutralizes lethal toxin in an in vitro assay of cytotoxicity, and find that it neutralizes LT by blocking the requisite cleavage of the amino-terminal 20 kD portion of the molecule (PA(20)) from the remainder of the PA monomer. We also demonstrate that the epitope recognized by this human monoclonal does not encompass the (166)RKKR(169) furin recognition sequence in domain 1 of PA.
目前批准的炭疽疫苗的主要免疫原性成分是二元毒素系统的保护性抗原（PA）单元。PA 特异性抗体中和炭疽毒素并预防感染。最近的研究确定，在人类中，只有针对特定决定簇的抗体能够实现毒素中和，并且这些抗体识别的中和表位分布在 PA 单体的整个表面。大多数这些表位实现中和的机制仍然未知。在本报告中，我们研究了一种针对 PA 氨基末端结构域的人源单克隆抗体在体外细胞毒性测定中中和致死毒素的过程，发现它通过阻止从 PA 单体的其余部分切割分子氨基末端 20kDa 部分（PA(20)）来中和 LT。我们还证明，该人源单克隆抗体识别的表位不包含 PA 结构域 1 中的（166）RKKR（169）furin 识别序列。
