Radiation protection with anti-radiation vaccine and anti-radiation antidote in reducing the biological impact of high dose and dose-rate, low-linear energy transfer radiation exposure.
Introduction: The prior development of radiation protection strategies included an anti-radiation vaccine and an anti-radiation hyperimmune serum, which demonstrated novel methods for both immunoprophylaxis and immunotherapy of acute radiation syndromes. Acute Radiation Disease (ARD) or Acute Radiation Syndrome (ARS), is defined as the collective toxic clinical state observed from the acute immunological and pathological processes observed in irradiated mammals, to include: systemic inflammatory response syndrome (SIRS), toxic multi-organ injury (TMOI), toxic multi-organ dysfunction syndromes (TMODS), and finally, toxic multi-organ failure (TMOF). Both high dose and high dose rate radiation induce apoptotic or necrotic cell death in radiosensitive cells, with the formation of radiation-induced toxins and their subsequent acute inflammatory processes. Radiation necrosis is the most severe form of radiation-induced injury, and when widespread, has challenging therapeutic implications. Existing principles for the treatment of acute radiation syndromes are based on the amelioration of progressive pathophysiological effects; however, replacement therapy does not always reduce potential lethality from acute, high dose exposure. Replacement therapies, which may include blood product transfusions and even blood marrow transplantation; were not completely effective for the clinical cases of ARS observed in exposed persons and animals after the Chernobyl Nuclear accident. Prior studies showed that mammalian tissues develop radiation-induced antigens after high dose exposures. These antigens are not recognized as self by the immune system, and therefore induce autoimmune reactions, including complement activation, and formation membrane attack complexes (MAC) which initiate a cascade of massive cell death. Methods: The MAC molecules are isolated from membranes of irradiated cells and are belongs a group of radiation-induced toxins (RIT) with antigenic properties that could correlate specifically with different forms of radiation disease. The molecular weight of the RIT group ranges from 200-250 kDa. These RIT, MAC-derived, molecules were isolated from the blood circulation, tissues or lymphatic systems of laboratory animals that were irradiated with doses known to induce the development of cerebral (MAC-1), non-specific toxic effects (MAC-2), gastrointestinal (MAC-3) and hematological (bone marrow) (MAC-4) syndromes. Results: Active immunization with MAC molecules, isolated from membranes of irradiated cells, administered to mammals before irradiation, increase survival rate among animals that were irradiated by lethal doses of gamma-radiation. The MAC molecules were isolated from cell membranes of different tissues and are specific to different forms of acute radiation sickness. Intramuscular or intraperitoneal injection of toxic doses of MAC antigens can induce signs and symptoms in radiation-naive animals similar to those observed in acute radiation syndromes, including death. Providing passive immunization, at variable periods of time post-radiation, with preparations of immune-globulins directed towards MAC molecules, can confer some protection against development of clinical sequelae in irradiated animals. Improved survival duration was observed in animals that received lower doses of the same MACs as a vaccine prior to LD90 irradiation. Therefore, active immunization can be induced by MAC molecules as a prophylaxis. The protective effects of the immunization begin to manifest 15-35 days after an injection of a biologically active MAC preparation. Conclusion: Our results suggest that a humanized 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.
43rd COSPAR Scientific Assembly. Held 28 January - 4 February
- Pub Date:
- January 2021