Baillie L W J
Biodefence Initiative, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, 21201, USA.
J Appl Microbiol. 2006 Sep;101(3):594-606. doi: 10.1111/j.1365-2672.2006.03112.x.
Anthrax is caused by the bacterium Bacillus anthracis. Although primarily a disease of animals, it can also infect man, sometimes with fatal consequences. As a result of concerns over the illicit use of this organism, considerable effort is focussed on the development of therapies capable of conferring protection against anthrax. This brief review will describe the efforts being made to address these issues.
A review of the literature and the proceedings of the sixth international conference on anthrax, held in Santa Fe, USA in 2005 shows intense activity, but there has been as yet no real progress. While effective antibiotics, antitoxins and vaccines are available, concerns over their toxicity and the emergence of resistant strains have driven the development of second-generation products. The principal target for vaccine development is Protective Antigen (PA), the nontoxic cell-binding component of anthrax lethal toxin. While the recombinant products currently undergoing human clinical trials will offer considerable advantages in terms of reduced side effects and ease of production, they would still require multiple, needle-based dosing, and the inclusion of the adjuvant alum makes them expensive to administer and stockpile. To address these issues, researchers are developing vaccine formulations, which stimulate rapid protection following needle-free injection (nasal, oral or transcutaneous), and are stable at room temperature to facilitate stockpiling and mass vaccination programs.
An array of medical countermeasures targeting B. anthracis will become available over the next 5-10 years.
The huge investment of research dollars is expected to dramatically expand the knowledge base. A better understanding of basic issues, such as survival in nature and pathogenesis in humans, will facilitate the development of new modalities to eliminate the threat posed by this organism.
炭疽病由炭疽杆菌引起。虽然它主要是一种动物疾病,但也可感染人类,有时会导致致命后果。由于担心该病原体被非法使用,人们将大量精力集中在开发能够提供炭疽防护的疗法上。本简要综述将描述为解决这些问题所做的努力。
对文献以及2005年在美国圣达菲举行的第六届炭疽国际会议的会议记录进行回顾,结果显示研究活动十分活跃,但尚未取得实际进展。虽然有有效的抗生素、抗毒素和疫苗,但对其毒性以及耐药菌株出现的担忧推动了第二代产品的研发。疫苗研发的主要靶点是保护性抗原(PA),它是炭疽致死毒素的无毒细胞结合成分。虽然目前正在进行人体临床试验的重组产品在减少副作用和易于生产方面具有相当大的优势,但它们仍需要多次通过针头注射给药,并且添加佐剂明矾使得给药和储存成本高昂。为了解决这些问题,研究人员正在开发疫苗制剂,这些制剂在无针注射(鼻内、口服或经皮)后能迅速提供保护,并且在室温下稳定,便于储存和大规模疫苗接种计划。
在未来5至10年内,一系列针对炭疽杆菌的医学应对措施将问世。
预计在研究资金上的巨额投入将极大地扩展知识基础。对诸如在自然界中的存活以及在人类中的发病机制等基本问题有更深入的了解,将有助于开发新的方法来消除该病原体所构成的威胁。