Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA.
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
J Med Microbiol. 2012 Oct;61(Pt 10):1380-1392. doi: 10.1099/jmm.0.045393-0. Epub 2012 Jul 5.
Current vaccine approaches to combat anthrax are effective; however, they target only a single protein [the protective antigen (PA) toxin component] that is produced after spore germination. PA production is subsequently increased during later vegetative cell proliferation. Accordingly, several aspects of the vaccine strategy could be improved. The inclusion of spore-specific antigens with PA could potentially induce protection to initial stages of the disease. Moreover, adding other epitopes to the current vaccine strategy will decrease the likelihood of encountering a strain of Bacillus anthracis (emerging or engineered) that is refractory to the vaccine. Adding recombinant spore-surface antigens (e.g. BclA, ExsFA/BxpB and p5303) to PA has been shown to augment protection afforded by the latter using a challenge model employing immunosuppressed mice challenged with spores derived from the attenuated Sterne strain of B. anthracis. This report demonstrated similar augmentation utilizing guinea pigs or mice challenged with spores of the fully virulent Ames strain or a non-toxigenic but encapsulated ΔAmes strain of B. anthracis, respectively. Additionally, it was shown that immune interference did not occur if optimal amounts of antigen were administered. By administering the toxin and spore-based immunogens simultaneously, a significant adjuvant effect was also observed in some cases. Thus, these data further support the inclusion of recombinant spore antigens in next-generation anthrax vaccine strategies.
目前针对炭疽病的疫苗方法是有效的;然而,它们仅针对在孢子发芽后产生的单一蛋白质(保护性抗原 (PA) 毒素成分)。PA 的产生随后在后期营养细胞增殖过程中增加。因此,可以改进疫苗策略的几个方面。包含与 PA 一起的孢子特异性抗原有可能诱导对疾病初始阶段的保护。此外,向当前疫苗策略中添加其他表位将降低遇到对疫苗有抵抗力的炭疽杆菌(新兴或工程)菌株的可能性。用重组孢子表面抗原(例如 BclA、ExsFA/BxpB 和 p5303)来增强 PA 的保护作用,已经在使用免疫抑制小鼠挑战来自减弱的 Sterne 株炭疽杆菌的孢子的挑战模型中得到证明。本报告利用豚鼠或小鼠分别用完全有毒的 Ames 株孢子或非毒性但被囊封的 ΔAmes 株炭疽杆菌的孢子进行的挑战,证明了类似的增强作用。此外,还表明如果给予最佳量的抗原,则不会发生免疫干扰。通过同时给予毒素和基于孢子的免疫原,在某些情况下还观察到显著的佐剂效应。因此,这些数据进一步支持在下一代炭疽疫苗策略中包含重组孢子抗原。