Maliev V, Popov D, Casey R C, Jones J A
Vladicaucasian Scientific Center, Russian Academy of Sciences, Biotechnology Departament, Russia.
Radiats Biol Radioecol. 2007 May-Jun;47(3):286-91.
The development of an anti-radiation vaccine could be very useful in reducing acute radiation syndromes. Existing principles for the treatment of acute radiation syndromes are based on the amelioration of progressive pathophysiological changes, using the concept of replacement therapy. Active immunization by small quantities of the essential radiation-induced systemic toxins of what we call the Specific Radiation Determinant (SRD) before irradiation increased duration of life among animals that were irradiated by lethal or sub-lethal doses of gamma-radiation. The SRD toxins possess antigenic properties that are specific to different forms of acute radiation sickness. Intramuscular injection of larger quantities of the SRD toxins induce signs and symptoms in irradiated naive animals similar to those observed in acute radiation syndromes, including death. Providing passive immunization, at variable periods of time following radiation, with preparations of immune-globulins directed at the SRD molecules, can confer some protection in the development of clinical sequelae in irradiated animals. Improved survival rates and times were observed in animals that received lower, sublethal doses of the same SRDs prior to irradiation. Therefore, active immunization can be induced by SRD molecules as a prophylaxis. The protective effects of the immunization begin to manifest 15-35 days after an injection of a biologically active SDR preparation. The SRD molecules are a group of radiation toxins with antigenic properties that correlate specifically with different forms of radiation disease. The SRD molecules are composed of glycoproteins and lipoproteins that accumulate in the lymphatic system of mammals in the first hours after irradiation, and preliminary analysis suggests that they may originate from cellular membrane components. The molecular weight of the SRD group ranges from 200-250 kDa. The SRD molecules were isolated from the lymphatic systems of laboratory animals that were irradiated with doses known to induce the development of cerebral (SRD-1), non-specific toxic effects (SRD-2), gastrointestinal (SRD-3) and hematological (bone marrow) (SRD-4) syndromes. Our results suggest that an anti-radiation vaccine can be developed for prophylactic use against radiation damage induced by acute exposure to significant doses of low Linear Energy Transfer (LET) radiation for humans, including nuclear power workers, commercial and military pilots, cosmonauts/astronauts, nuclear-powered engine vessel operators and possibly even the civilian population in the case of a nuclear terrorism event.
开发一种抗辐射疫苗对于减轻急性放射综合征可能非常有用。现有的急性放射综合征治疗原则基于采用替代疗法改善渐进性病理生理变化。在照射前通过小剂量我们所称的特异性辐射决定因素（SRD）这种基本的辐射诱导全身毒素进行主动免疫，可延长接受致死或亚致死剂量γ射线照射动物的寿命。SRD毒素具有针对不同形式急性放射病的特异性抗原特性。向未受照射的动物肌肉注射大量SRD毒素会诱发与急性放射综合征中观察到的类似体征和症状，包括死亡。在辐射后的不同时间段，用针对SRD分子的免疫球蛋白制剂进行被动免疫，可在受照射动物临床后遗症的发展中提供一定保护。在照射前接受较低亚致死剂量相同SRD的动物中观察到存活率和存活时间有所提高。因此，SRD分子可诱导主动免疫作为预防措施。免疫的保护作用在注射生物活性SDR制剂后15 - 35天开始显现。SRD分子是一组具有抗原特性的辐射毒素，与不同形式的辐射疾病特异性相关。SRD分子由糖蛋白和脂蛋白组成，在照射后的最初几小时内积聚在哺乳动物的淋巴系统中，初步分析表明它们可能源自细胞膜成分。SRD组的分子量范围为200 - 250 kDa。SRD分子是从接受已知可诱发脑（SRD - 1）、非特异性毒性作用（SRD - 2）、胃肠道（SRD - 3）和血液学（骨髓）（SRD - 4）综合征剂量照射的实验动物的淋巴系统中分离出来的。我们的结果表明，可以开发一种抗辐射疫苗用于预防人类因急性暴露于大量低线性能量传递（LET）辐射（包括核电工作者、商业和军事飞行员、宇航员、核动力发动机船只操作员，甚至在核恐怖主义事件情况下的平民）所导致的辐射损伤。
