EVALUATION OF THE ROLE OF THE MICROBIOTA IN THE DEVELOPMENT OF THE IMMUNE RESPONSE AFTER VACCINATION, USING PIGS AS ANIMAL MODEL

THE PRESENT PROJECT AIMS TO DETERMINE THE EFFECT THAT THE ALTERATION OF THE MICROBIOTA, RESULTING FROM AN ANTIBIOTIC TREATMENT, IN RECENTLY WEANED PIGS MAY HAVE ON THE DEVELOPMENT OF SPECIFIC IMMUNITY AFTER VACCINATION AND ULTERIOR REVACCINATION. THE PROJECT IS CHARACTERIZED BY THE INTEGRATION OF ANALYSIS OF THE MICROBIOME WITH THE IMMUNE RESPONSE, EXAMINED IN DIFFERENT WAYS. IN DIFFERENT EXPERIMENTS, DIFFERENT ROUTES OF ADMINISTRATION (INTRAMUSCULAR AND INTRANASAL) OF THE VACCINE AND DIFFERENT FORMULATIONS (INACTIVATED AND LIVE ATTENUATED VACCINE) WILL BE COMPARED. THE VACCINE MODEL CHOSEN IS THAT OF AUJESZKY'S DISEASE OR PSEUDORABIES, SINCE THE CORRELATES OF PROTECTION ARE WELL KNOWN, ATTENUATED AND INACTIVATED VACCINES ARE AVAILABLE, THE RESPONSE TO INTRAMUSCULAR AND INTRANASAL VACCINATION IS WELL CHARACTERIZED, AND THE DISEASE IS ABSENT IN OUR COUNTRY, ALTHOUGH THE VACCINATION IS MANDATORY. THESE CIRCUMSTANCES ALLOW US TO HAVE A SIMPLER INTERPRETATION MODEL WITH PRACTICAL RELEVANCE. CHANGES IN THE MICROBIOTA AFTER TREATMENT AND SUBSEQUENT MICROBIAL REPOPULATION THROUGHOUT THE EXPERIMENT WILL BE ASSESSED USING METAGENOMIC TECHNIQUES (SHOTGUN SEQUENCING). THE IMMUNE RESPONSE OF VACCINATED ANIMALS WILL BE ASSESSED THROUGH THE MEASUREMENT OF VIRUS-SPECIFIC ANTIBODIES AND CELL MEDIATED IMMUNITY. LIKEWISE, TRANSCRIPTOMICS OF PERIPHERAL BLOOD MONONUCLEAR CELLS WILL BE PERFORMED IN THE FIRST 7 DAYS AFTER VACCINATION TO DETERMINE (BLOOD TRANSCRIPTIONAL MODULES) WHICH AREAS OR ASPECTS OF THE INITIAL INNATE OR SPECIFIC IMMUNE RESPONSE ARE AFFECTED BY THE CHANGES INDUCED IN THE MICROBIOTA. FINALLY, THE IMPACT ON ANAMNESTIC RESPONSES WILL BE EXAMINED. IN THE INTRANASAL VACCINATION MODEL, THE EFFECT OF A SYSTEMIC ANTIBIOTIC TREATMENT WILL BE EXAMINED, WHICH WILL AFFECT THE INTESTINAL AND NASAL MICROBIOTA, IN COMPARISON WITH A SYSTEMICALLY NON-ABSORBABLE ORAL TREATMENT, WHICH SHOULD MAKE IT POSSIBLE TO DETERMINE THE ROLE OF THE NASAL MICROBIOTA IN THE ESTABLISHMENT OF IMMUNITY WHEN VACCINES ARE APPLIED THIS WAY. IN GENERAL, IT IS EXPECTED THAT THE RESULTS ALLOW, TO THE LESSER EXTENT, THE IDENTIFICATION OF THE MICROBIAL SPECIES OR TAXA THAT MAY BE INVOLVED IN A BETTER OR WORSE RESPONSE TO VACCINATION, AS WELL AS THE IDENTIFICATION OF WHICH SPECIFIC ASPECTS OF THE IMMUNE RESPONSE ARE AFFECTED BY CHANGING THE MICROBIOTA.