Use of a Staphylococcus aureus Conjugate Vaccine in Patients Receiving Hemodialysis
Henry Shinefield, M.D., Steven Black, M.D., Ali Fattom, Ph.D., Gary Horwith, M.D., Scott Rasgon, M.D., Juan Ordonez, M.D., Hock Yeoh, M.D., David Law, M.D., John B. Robbins, M.D., Rachel Schneerson, M.D., Larry Muenz, Ph.D., Steve Fuller, Ph.D., Joanie Johnson, R.N., Bruce Fireman, M.A., Harry Alcorn, Pharm.D., and Robert Naso, Ph.D.
Background In patients with decreased resistance to infection,Staphylococcus aureus is a major cause of bacteremia and itscomplications. The capsular polysaccharides are essential forthe pathogenesis of and immunity to S. aureus infection andare targets for vaccines.
Methods In a double-blind trial involving patients with end-stagerenal disease who were receiving hemodialysis, we evaluatedthe safety, immunogenicity, and efficacy of a vaccine with S.aureus type 5 and 8 capsular polysaccharides conjugated to nontoxicrecombinant Pseudomonas aeruginosa exotoxin A. Between April1998 and August 1999, 1804 adult patients at 73 hemodialysiscenters were randomly assigned to receive a single intramuscularinjection of either vaccine or saline. IgG antibodies to S.aureus type 5 and 8 capsular polysaccharides were measured forup to two years, and episodes of S. aureus bacteremia were recorded.Efficacy was estimated by comparing the incidence of S. aureusbacteremia in the patients who received the vaccine with theincidence in the control patients.
Results Reactions to the vaccine were generally mild to moderate,and most resolved within two days. The capsular polysaccharideselicited an antibody response of at least 80 µg per milliliter(the estimated minimal level conferring protection) in 80 percentof patients for type 5 and in 75 percent of patients for type8. The efficacy during weeks 3 to 54 was only 26 percent (P=0.23).However, between weeks 3 and 40 after vaccination, S. aureusbacteremia developed in 11 of 892 patients in the vaccine groupwho could be evaluated for bacteremia, as compared with 26 of906 patients in the control group (estimate of efficacy, 57percent; 95 percent confidence interval, 10 to 81 percent; nominalP=0.02).
Conclusions In patients receiving hemodialysis, a conjugatevaccine can confer partial immunity against S. aureus bacteremiafor approximately 40 weeks, after which protection wanes asantibody levels decrease.
Source Information
From the Kaiser Permanente Vaccine Study Center, Oakland, Calif. (H.S., S.B., J.O., D.L.); Nabi, Rockville, Md. (A.F., G.H., R.N.); Southern California Kaiser Permanente, Los Angeles (S.R., H.Y.); the National Institute of Child Health and Human Development, Bethesda, Md. (J.B.R., R.S.); and Larry Muenz and Associates, Rockville, Md. (L.M.). Other authors were Steve Fuller, Ph.D., Nabi, Rockville, Md.; Joanie Johnson, R.N., and Bruce Fireman, M.A., Kaiser Permanente, Oakland, Calif.; and Harry Alcorn, Pharm.D., Total Renal Research, Minneapolis.
Address reprint requests to Dr. Shinefield at the Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, 16th Fl., Oakland, CA 94612, or at henry.shinefield{at}kp.org.
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