Rhodococcus equi is a facultative intracellular pathogenic bacterium that causes a form of pneumonia similar to tuberculosis in foals and immunocompromised humans. A vaccine against R. equi is lacking. We studied the efficacy of maternal vaccination with deacetylated poly-N-acetyl glucosamine (dPNAG) oligosaccharide conjugated to tetanus toxoid to protect foals against R. equi. Pregnant mares (n=9) were randomly assigned to intramuscular injection 6 and 3 weeks prior to foaling with either vaccine (n=5) or saline (n=4). Foals were infected intrabronchially at age 28 days with 1 106 of a single strain of live, virulent R. equi. Foals were examined twice daily for clinical signs of R. equi pneumonia (viz., coughing, tachypnea, dyspnea, temperature <103F), and weekly by thoracic ultrasonography. Blood samples were collected at age 2, 14, 28, 42, 56, and 84 days from all foals to detect antibodies by ELISA against dPNAG and native PNAG in serum and IFN production from peripheral blood mononuclear cells (PBMCs). The proportion of foals with pneumonia was significantly (P>0.05) greater among the unvaccinated mares (3/4) than vaccinated mares (0/5). Titers of dPNAG and PNAG antibodies were significantly (P>0.05) higher at all ages for foals of vaccinated mares. IFN produced by PBMCs stimulated with R. equi antigen was significantly greater (P>0.05) at age 28 days (prior to infection) in foals of vaccinated mares. Results indicate the dPNAG vaccine protected foals against the intracellular pathogen R. equi and efficacy against R. equi was likely mediated by maternally-transferred antibodies and enhanced CMI responses, and contribute to a growing body of evidence for a key role of antibodies in protecting against intracellular pathogens.