Antiradiation vaccine: Technology development of prophylaxis, prevention and treatment of biological sequelae from neutron irradiation.

Dmitri Popov1, Jeffrey Jones2 Slava Maliev3 1- Advanced Medical Technology and Systems Inc., Toronto, Ontario, Canada 2- NASA/ Lyndon B. Johnson Space Center, Houston, TX 3- Russian Academy of Science, District Department, Biotectnology Division, Vladicaucas, North Osetia, Russia. Introduction: The efficacy of an anti-radiation vaccine for the prophylaxis, prevention and therapy of acute radiation pathology was studied in a neutron exposure facility. The biological effects of fast neutrons include damage of the central nervous system and cardiovascular system with development of the cerebrovascular form of acute radiation syndrome. This is a result of the formation of neurotoxins in the central nervous system of irradiated animals after high doses of fast neutron exposure. Neutron irradiation generated cerebrovascular and cardiovascular radiation toxins (neurotoxins) which induce the development of clinical symptoms, syndromes and underlying pathophysiologic processes. Current methods of radiation protection and acute medical management are not effective against moderate and high doses of neutron irradiation. A novel vaccine against radiation-induced systemic toxins may be a more effective radioprotectant against high doses of gamma-radiation. The antigens for the vaccine are derived from neuro- and cyto-toxins isolated from the central lymphatics of gammairradiated animals. Methods : 1) Prepare antiradiation vaccine i) Isolate radiation toxins from irradiated animals, ii) admix a toxoid from the various radiotoxin types (SRD- Specific Radiation Determinant groups) which include: cerebrovascular neurotoxin, cardiovascular toxin, gastrointestinal toxin, and hematopoietic hematotoxin. iii) immunize the animals with vehicleonly in placebo and toxoid-containing vaccine in the experimental group. 2) Neutron exposure at the Scientific Research Institute of Nuclear Physics, Dubna, Russia, employing the research reactor BBP-M, generating a mixed neutron beam contained 95 % fast neutron irradiation and 5% gamma-irradiation. Neutron energy 1.98 2.30 Me- V energy; Dose/Dose rate 10.7 Gy, at 0.22 Gy/min. 3) Experimental Design: Group A Controls- 5 rabbits ; Group B Placebo vaccine- 5 rabbits; Group C Experimental- radioprotectant Cystamine (50 mg/kg)-5 and 15 minutes before irradiation)- 5 rabbits. Group D Experimental- radioprotectant Mexamine (10 mg/kg) 15 minutes before irradiation- 5 rabbits; Group E Experimental- antiradiation vaccine: subcutaneous or intramuscular administration - 2 ml of active toxoid, 2 months before irradiation. Results: Group A 100% mortality within two hours after neutron irradiation with clinical symptoms of acute cerebrovascular syndrome. Group B 100% mortality less than 2 hours following irradiation. Group C 100% mortality within 8-10 hours after irradiation. Group D 100% mortality within 11 hours after irradiation. In groups A- D the development of acute radiation cerebrovascular syndrome produced rapid death. Group E - 100% mortality by 240 hours (10 days) following neutron irradiation with animals exhibiting a combination or individual forms of acute cerebrovascular cardiovascular, and gastrointestinal clinical syndromes. Discussion: A pre-irradiation radiation-toxoid vaccine significantly prolonged the survival of rabbits exposed to a high dose 1LD100 of neutron radiation from two hours in controls to 11 days. We postulate that the radiation toxins of SRD group isolated from the lymph of gamma-

irradiated animals are likely similar in structure to radiation toxins generated and circulated in the blood and lymph of neutron-irradiated animals. However, preliminary studies indicate that the toxico- kinetics and -dynamics of radiation toxins of the various SRD groups generated following neutron-irradiation are likely different from those following gamma-irradiation. Yet, the technology to develop a more effective vaccine to reduce radiation-induced toxicity, merits further investigation.