Descripción del proyecto
TO PREVENT VIRAL DISEASE OUTBREAKS, VACCINATION IS ONE OF THE MAIN METHODS AVAILABLE FOR SUSTAINABLE AQUACULTURE, HOWEVER, UP TO NOW AND DESPITE DECADES OF EFFORTS, FEW EFFICIENT AND LONG-TERM PROTECTIVE VIRAL VACCINES (I,E: DNA VACCINES AGAINST NOVIRHABDOVIRUSES) HAVE BEEN DEVELOPED FOR PRACTICAL USE, ONE OF THE REASONS FOR THOSE FAILURES MIGHT BE DUE TO THE FACT THAT ONLY CONVENTIONAL MAMMALIAN KNOWLEDGE OF ADAPTIVE IMMUNE RESPONSES HAVE BEEN EMPLOYED FOR FISH VACCINE DESIGN, HOWEVER, IT IS UNKNOWN HOW APPLICABLE IS THIS INFORMATION TO FISH, SINCE FISH RELY MORE HEAVYLY ON THEIR INNATE RATHER THAN IN THEIR ADAPTIVE RESPONSES, FURTHERMORE, IN FISH THERE IS NO IGG SWITCH, NOR IGM MATURATION AND ONLY 50% OF SURVIVORS TO VIRAL INFECTIONS SHOW NEUTRALIZING ANTIBODIES, SUGGESTING THAT ALTERNATIVE MECHANISMS FOR LONG-TERM PROTECTION SUCH AS UNKNOWN INNATE RESPONSES, MIGHT BE IMPORTANT, ON THE OTHER HAND, RECENTLY DESCRIBED MAMMALIAN B/T CELL-INDEPENDENT LONG-TERM MEMORY RESPONSES (TRAINED IMMUNITY, TI), LIKE THOSE EXISTING IN PLANTS AND INVERTEBRATES, HAVE NOT BEEN EXPLORED YET IN FISH, THEREFORE, MODULATING FISH TI MAY REPRESENT AN INNOVATIVE AND GROUND-BREAKING REVOLUTION IN THE DESIGN OF XXI CENTURY AQUACULTURE VACCINES AND MIGHT EVEN ALLOW FOR THE IDENTIFICATION OF NOVEL IMMUMODULATORY/THERAPEUTIC AGENTS, COULD TI BE THE KEY TO SOLVE THE PRESENT PUZZLES OF FISH VIRAL VACCINATION?, TO ANSWER THIS AND OTHER RELATED QUESTIONS, THE MAIN OBJECTIVE OF THIS PROPOSAL IS THE STUDY OF FISH TI AS WELL AS ITS POSSIBLE APPLICATIONS TO THE DEVELOPMENT OF VACCINES AND/OR IMMUNOMODULATORY/THERAPEUTIC AGENTS, IN ORDER TO DEVELOP THIS MAIN OBJECTIVE, WE HAVE DESIGNED AN STRATEGY COORDINATED BY 3 RESEARCH GROUPS FROM DIFFERENT INSTITUTIONS (UMH, INIA, CSIC) WITH AN ONGOING EXPERIENCE OF COMPLEMENTARY COOPERATION IN FISH IMMUNOLOGY/VIROLOGY/VACCINALOGY, BASED UPON THE FOLLOWING SPECIFIC OBJECTIVES: 1,-INVESTIGATING THE MAIN TRAITS DEFINING FISH VIRAL TRAINED IMMUNITY AND REPROGRAMMING DURING VIRAL INFECTION/VACCINATION, 2,- IDENTIFYING TRAINED IMMUNITY MOLECULES BY USING VIRAL PROTEINS (VP) AND FISH MULTIPATH GENES (MPG), 3,- IDENTIFYING MEMORY CELLS IN THE IMMUNITY INNATE SYSTEM AND THEIR RESPONSES AGAINST THE VIRAL INFECTION, 4,- AQUACULTURE APPLICATIONS OF THE IDENTIFIED MOLECULES AS IMMUNOMODULATORS, THERAPEUTIC AGENTS AND VACCINES, TO DEVELOP OBJECTIVES 1, 2 AND 3 THE ZEBRAFISH (DANIO RERIO, ZF) HAS BEEN CHOSEN AS THE MODEL FISH SPECIE SINCE B/T CELL-DEFICIENT RAG1-/- MUTANTS ARE AVAILABLE AND THEREFORE, B/T CELL-INDEPENDENT MEMORY (TI) RESPONSES CAN BE BEST STUDIED IN THESE FISH, TO TRANSFER THE TI KNOWLEDGE OBTAINED IN ZF TO FISH CULTURED SPECIES, THE FRESH WATER RAINBOW TROUT (ONCORHYNCHUS MYKISS) AND THE MARINE WATER TURBOT (SCOPTHALMUS MAXIMUS) HAVE BEEN CHOSEN, PECES\VIRUS\VACUNAS\TRAINED IMMUNITY\SISTEMA INMUNE INNATO\MICROARRAYS