**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** RHODOCOCCUS EQUI (R. EQUI) IS A BACTERIUM THAT CAUSES A PROGRESSIVE, INSIDIOUS, AND DEVASTATING FORM OF PNEUMONIA IN FOALS THAT IS BOTH A THREAT TO THEIR WELFARE AND DETRIMENTAL TO THE EQUINE INDUSTRY. R. EQUI MAY EITHER CONTAIN OR LACK A PROTEIN IN THEIR SURFACE CALLED VIRULENCE ASSOCIATED PROTEIN A, WHICH ENABLES THE BACTERIUM TO SURVIVE AND MULTIPLY INSIDE THE CELLS CAUSING PNEUMONIA; THESE ARE CALLED VIRULENT OR AVIRULENT R. EQUI, RESPECTIVELY. TO DATE, NO VACCINE AGAINST THIS DISEASE IS AVAILABLE COMMERCIALLY, BUT ADMINISTRATION OF VIRULENT R. EQUI IN THE STOMACH OF FOALS CAN PREVENT SUBSEQUENT INFECTION IN THE LUNGS. THE LONG-TERM GOAL OF OUR PROJECT IS TO DEVELOP PREVENTATIVE STRATEGIES TO PROTECT FOALS AGAINST R. EQUI PNEUMONIA, AND THE SHORT-TERM GOAL IS TO DETERMINE WHETHER GIVING FOALS EITHER VIRULENT OR AVIRULENT R. EQUI, OR AN IMMUNOSTIMULANT (CALLED CPG), WILL INDUCE PROTECTION AGAINST SUBSEQUENT INFECTION WITH R. EQUI BY GENERATING CELLS THAT ARE MORE EFFICIENT AT KILLING BACTERIA (CALLED TRAINED CELLS). THE OBJECTIVES OF OUR PROJECT ARE: 1) TO DEMONSTRATE THAT ADMINISTRATION OF EITHER VIRULENT OR AVIRULENT R. EQUI OR CPG PROTECTS FOALS AGAINST R. EQUI PNEUMONIA; AND, 2) TO DETERMINE THE EFFECTS OF THESE SUBSTANCES IN THE EXPRESSION OF GENES IN A TYPE OF WHITE BLOOD CELLS (CALLED MONOCYTES), AND THEIR PRECURSORS IN THE BONE MARROW (CALLED MYELOID PROGENITOR CELLS). WE EXPECT TO LEARN WHETHER THIS PROCEDURE WILL PROTECT THEM AGAINST PNEUMONIA BY INDUCING TRAINING OF CELLS (A PROCESS CALLED TRAINED IMMUNITY). THE IMPACT OF THIS PROJECT IS THAT IT WILL ADVANCE THE RESEARCH FIELDS OF TRAINED IMMUNITY AND PREVENTION OF INFECTIOUS DISEASES IN FOALS, AS WELL AS GENERATE USEFUL INFORMATION FOR DESIGNING EFFECTIVE VACCINE COMPONENTS (INNATE IMMUNE ADJUVANTS).