Brey Robert N
DOR BioPharma, Inc., 1691 Michigan Avenue, Suite 435, Miami, FL 33139, USA.
Adv Drug Deliv Rev. 2005 Jun 17;57(9):1266-92. doi: 10.1016/j.addr.2005.01.028. Epub 2005 Apr 21.
The current vaccine for anthrax has been licensed since 1970 and was developed based on the outcome of human trials conducted in the 1950s. This vaccine, known as anthrax vaccine adsorbed (AVA), consists of a culture filtrate from an attenuated strain of Bacillus anthracis adsorbed to aluminum salts as an adjuvant. This vaccine is considered safe and effective, but is difficult to produce and is associated with complaints about reactogenicity among users of the vaccine. Much of the work in the past decade on generating a second generation vaccine is based on the observation that antibodies to protective antigen (PA) are crucial in the protection against exposure to virulent anthrax spores. Antibodies to PA are thought to prevent binding to its cellular receptor and subsequent binding of lethal factor (LF) and edema factor (EF), which are required events for the action of the two toxins: lethal toxin (LeTx) and edema toxin (EdTx). The bacterial capsule as well as the two toxins are virulence factors of B. anthracis. The levels of antibodies to PA must exceed a certain minimal threshold in order to induce and maintain protective immunity. Immunity can be generated by vaccination with purified PA, as well as spores and DNA plasmids that express PA. Although antibodies to PA address the toxemia component of anthrax disease, antibodies to additional virulence factors, including the capsule or somatic antigens in the spore, may be critical in development of complete, sterilizing immunity to anthrax exposure. The next generation anthrax vaccines will be derived from the thorough understanding of the interaction of virulence factors with human and animal hosts and the role the immune response plays in providing protective immunity.
目前的炭疽疫苗自1970年获得许可，是基于20世纪50年代进行的人体试验结果开发的。这种疫苗称为吸附炭疽疫苗（AVA），由减毒炭疽芽孢杆菌的培养滤液吸附到铝盐作为佐剂组成。这种疫苗被认为是安全有效的，但生产困难，并且疫苗使用者中存在关于反应原性的投诉。过去十年中，许多关于第二代疫苗的研究工作是基于这样的观察结果：针对保护性抗原（PA）的抗体在预防暴露于有毒炭疽孢子方面至关重要。针对PA的抗体被认为可以阻止其与细胞受体结合，以及随后致死因子（LF）和水肿因子（EF）的结合，这是两种毒素（致死毒素（LeTx）和水肿毒素（EdTx））发挥作用所必需的事件。细菌荚膜以及这两种毒素是炭疽芽孢杆菌的毒力因子。针对PA的抗体水平必须超过一定的最低阈值，才能诱导和维持保护性免疫。通过接种纯化的PA以及表达PA的孢子和DNA质粒可以产生免疫力。虽然针对PA的抗体解决了炭疽病的毒血症成分，但针对其他毒力因子（包括孢子中的荚膜或体细胞抗原）的抗体，可能在对炭疽暴露产生完全的杀菌免疫方面至关重要。下一代炭疽疫苗将源于对毒力因子与人和动物宿主相互作用以及免疫反应在提供保护性免疫中所起作用的深入理解。
