Department of Pathology, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Bacterial Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Host Microbe. 2012 Jul 19;12(1):117-124. doi: 10.1016/j.chom.2012.05.011.
Although pathogen inactivation by γ-radiation is an attractive approach for whole-organism vaccine development, radiation doses required to ensure sterility also destroy immunogenic protein epitopes needed to mount protective immune responses. We demonstrate the use of a reconstituted manganous peptide complex from the radiation-resistant bacterium Deinococcus radiodurans to protect protein epitopes from radiation-induced damage and uncouple it from genome damage and organism killing. The Mn(2+) complex preserved antigenic structures in aqueous preparations of bacteriophage lambda, Venezuelan equine encephalitis virus, and Staphylococcus aureus during supralethal irradiation (25-40 kGy). An irradiated vaccine elicited both antibody and Th17 responses, and induced B and T cell-dependent protection against methicillin-resistant S. aureus (MRSA) in mice. Structural integrity of viruses and bacteria are shown to be preserved at radiation doses far above those which abolish infectivity. This approach could expedite vaccine production for emerging and established pathogens for which no protective vaccines exist.
虽然通过γ辐射使病原体失活是开发全生物体疫苗的一种有吸引力的方法，但确保无菌所需的辐射剂量也会破坏产生保护性免疫反应所需的免疫原性蛋白表位。我们证明了使用来自抗辐射细菌 Deinococcus radiodurans 的重组锰肽复合物来保护蛋白表位免受辐射诱导的损伤，并将其与基因组损伤和生物体杀伤脱耦。在超致死辐射（25-40 kGy）下，Mn(2+) 复合物在噬菌体 λ、委内瑞拉马脑炎病毒和金黄色葡萄球菌的水制剂中保存了抗原结构。辐照疫苗引发了抗体和 Th17 反应，并在小鼠中诱导了针对耐甲氧西林金黄色葡萄球菌（MRSA）的 B 和 T 细胞依赖性保护。结果表明，病毒和细菌的结构完整性在远远超过消除感染力的辐射剂量下得以保留。这种方法可以加快针对新兴和已建立的病原体的疫苗生产，而这些病原体目前尚无有效的疫苗。
