Blood transfusion recipients are at risk of virus transmission, with hepatitis virus remaining the most frequent; however, the spread of AIDS into the general donor population raises fears concerning future HIV risk and risk from unidentified viruses. Our objective is to develop methods of virus sterilization, applicable to red cell (RBCC) and platelet concentrates (PC), which will eliminate this risk. Research will emphasize photosensitizers, especially aluminum phthalocyanine (AIPc) derivatives for the treatment of RBCC and PC, and psoralens for the treatment of PC. Current favorable results with sulfonated AIPc will be compared with positively charged and amphoteric phthalocyanines. Each has shown superior reactivity in other biological systems. Current results with AMT (a positively charged psoralen) will be extended. Attention will focus on the use of quenchers of hydroxyl radicals and other """"""""type l"""""""" reactants, which were recently shown to be advantageous in eliminating undesired side reactions observed with both photodynamic dyes and psoralens - without reducing the rate or extent of virus kill. Quenchers which scavenge both type l radicals and singlet oxygen will also be tested. Virus killing will be measured with vesicular stomatitis virus (and other marker viruses), HIV, and hepatitis C virus. Measurements of nucleic acid modification will also be made. Red cell and platelet integrity will be monitored immediately following treatment and on storage under standard blood bank conditions. Measurements will include hemoglobin release, K+ leakage, IgG binding, metabolic indicators such as glucose utilization, intracellular ATP and 2,3-DPG for RBC, and changes in platelet number, morphology, pH, aggregation response, and appearance/disappearance of selected membrane antigens, and the ability to correct an aspirin-induced thrombocytopathy in baboons. For both RBCC and PC, circulatory recovery and half-life, will be evaluated following autologous transfusion in rabbits and baboons. Neoimmunogenicity will be assessed in these baboon studies and also in a rabbit model using human RBCC and PC. Available information regarding the toxicology of compounds giving favorable results will be reviewed, and Ames testing performed.
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