Mechanisms of action for an anti-radiation vaccine in reducing the biological impact of high dose and dose-rate, low-linear energy transfer radiation exposure.
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.
Maliev
V
V
Vladicaucasian Scientific Center, Russian Academy of Sciences, Biotechnology Departament, Russia.
Popov
D
D
Casey
R C
RC
Jones
J A
JA
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000302:isolation & purification / Q000627:therapeutic use*; D000818:Animals; D000941:Antigens / Q000276:immunology; D002417:Cattle; D004285:Dogs; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006736:Horses; D016233:Immunotherapy, Active / Q000379:methods*; D018499:Linear Energy Transfer; D008198:Lymph Nodes / Q000737:chemistry / Q000276:immunology; D051379:Mice; D011817:Rabbits; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000276:immunology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D051381:Rats; D012756:Sheep; D013552:Swine
D000276:Adjuvants, Immunologic; D000941:Antigens; D011837:Radiation-Protective Agents