Kaur Manpreet, Chug Hema, Singh Harpreet, Chandra Subhash, Mishra Manish, Sharma Meenakshi, Bhatnagar Rakesh
Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, Delhi, India.
Mol Immunol. 2009 Jun;46(10):2107-15. doi: 10.1016/j.molimm.2008.12.031. Epub 2009 Apr 7.
Bacillus anthracis is the etiological agent of anthrax. Protective antigen (PA) has been established as the key protective immunogen and is the major component of anthrax vaccine. Prior studies have indicated that C-terminus host cell receptor binding region contains dominant protective epitopes of PA. In the present study, we focused our attention on determining B-cell epitopes from this region, which could be employed as a vaccine. Using B-cell epitope prediction systems, three regions were identified; ID-I: 604-622, ID-II: 626-676 and ID-III: 707-723 aa residues. These epitopes elicited potent B-cell response in BALB/c mice. ID-II in particular was found to be highly immunogenic in terms of IgG antibody titre, with a predominantly IgG1/IgG2a subclass distribution indicating Th2 bias and high affinity/avidity index. Effective cellular immunity was additionally generated which also signified its Th2 bias. Further, ID-II induced high level of lethal toxin neutralizing antibodies and robust protective immunity (66%) against in vivo lethal toxin challenge. Thus, ID-II can be classified as an immunodominant B-cell epitope and may prove significant in the development of an effective immunoprophylactic strategy against anthrax.
炭疽芽孢杆菌是炭疽病的病原体。保护性抗原（PA）已被确立为关键的保护性免疫原，是炭疽疫苗的主要成分。先前的研究表明，C末端宿主细胞受体结合区域包含PA的主要保护性表位。在本研究中，我们重点关注确定该区域可作为疫苗使用的B细胞表位。使用B细胞表位预测系统，确定了三个区域；ID-I：604-622，ID-II：626-676和ID-III：707-723个氨基酸残基。这些表位在BALB/c小鼠中引发了强烈的B细胞反应。特别是ID-II，就IgG抗体滴度而言具有高度免疫原性，其主要为IgG1/IgG2a亚类分布，表明存在Th2偏向以及高亲和力/亲合力指数。此外还产生了有效的细胞免疫，这也表明其存在Th2偏向。此外，ID-II诱导产生了高水平的致死毒素中和抗体以及针对体内致死毒素攻击的强大保护性免疫（66%）。因此，ID-II可被归类为免疫显性B细胞表位，可能在开发针对炭疽的有效免疫预防策略中具有重要意义。
