BACKGROUND Staphylococcus aureus, the first or second most common pathogen isolated from patients, is capsulated; there are at least 12 capsular types, and types 5 and 8 comprise approximately 85% of blood. Types 5 and 8, composed of a trisaccharide repeat unit including a mannose uronic acid and 2 fucoses, are non-immunogenic. As protein conjugates, they induce opsonophagocytic antibodies that confer type-specific active and passive protection in mice. METHODS A phase II study of patients with end-stage renal disease showed that these conjugates induced approximately one third of the immunoglobulin G antibody of healthy individuals. Increasing the dose to 100 microg of polysaccharide induced levels similar to that in healthy individuals injected with 25 microg. RESULTS In a double-blinded randomized and controlled study of patients undergoing renal dialysis, the conjugates induced statistically significant protection against bacteremia for as long as 10 months after immunization. The estimated protective level was 80 microg Ab/mL. At re-injection approximately 2 years later, 83 of 83 recipients responded with protective levels. CONCLUSIONS Conjugate vaccine-induced antibodies to the types 5 and 8 capsular polysaccharide antibodies of S aureus prevent bacteremia caused by this pathogen. The extent and duration of conjugate-induced immunity can be extended by re-immunization approximately 1 year later. Studies of patients undergoing cardiovascular surgery who would be immunized with the staphylococcus conjugates when they are immunologically intact are planned.