在接受血液透析的患者中使用金黄色葡萄球菌结合疫苗。

Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis.

作者信息

Shinefield Henry, Black Steven, Fattom Ali, Horwith Gary, Rasgon Scott, Ordonez Juan, Yeoh Hock, Law David, Robbins John B, Schneerson Rachel, Muenz Larry, Fuller Steve, Johnson Joanie, Fireman Bruce, Alcorn Harry, Naso Robert

机构信息

Kaiser Permanente Vaccine Study Center, Oakland, CA 94612, USA.

出版信息

N Engl J Med. 2002 Feb 14;346(7):491-6. doi: 10.1056/NEJMoa011297.

DOI:10.1056/NEJMoa011297

PMID:11844850

Abstract

BACKGROUND

In patients with decreased resistance to infection, Staphylococcus aureus is a major cause of bacteremia and its complications. The capsular polysaccharides are essential for the pathogenesis of and immunity to S. aureus infection and are targets for vaccines.

METHODS

In a double-blind trial involving patients with end-stage renal disease who were receiving hemodialysis, we evaluated the safety, immunogenicity, and efficacy of a vaccine with S. aureus type 5 and 8 capsular polysaccharides conjugated to nontoxic recombinant Pseudomonas aeruginosa exotoxin A. Between April 1998 and August 1999, 1804 adult patients at 73 hemodialysis centers were randomly assigned to receive a single intramuscular injection of either vaccine or saline. IgG antibodies to S. aureus type 5 and 8 capsular polysaccharides were measured for up to two years, and episodes of S. aureus bacteremia were recorded. Efficacy was estimated by comparing the incidence of S. aureus bacteremia in the patients who received the vaccine with the incidence in the control patients.

RESULTS

Reactions to the vaccine were generally mild to moderate, and most resolved within two days. The capsular polysaccharides elicited an antibody response of at least 80 microg per milliliter (the estimated minimal level conferring protection) in 80 percent of patients for type 5 and in 75 percent of patients for type 8. The efficacy during weeks 3 to 54 was only 26 percent (P=0.23). However, between weeks 3 and 40 after vaccination, S. aureus bacteremia developed in 11 of 892 patients in the vaccine group who could be evaluated for bacteremia, as compared with 26 of 906 patients in the control group (estimate of efficacy, 57 percent; 95 percent confidence interval, 10 to 81 percent; nominal P=0.02).

CONCLUSIONS

In patients receiving hemodialysis, a conjugate vaccine can confer partial immunity against S. aureus bacteremia for approximately 40 weeks, after which protection wanes as antibody levels decrease.

摘要

背景

在抗感染能力下降的患者中，金黄色葡萄球菌是菌血症及其并发症的主要病因。荚膜多糖对于金黄色葡萄球菌感染的发病机制和免疫反应至关重要，并且是疫苗的作用靶点。

方法

在一项双盲试验中，我们评估了一种将5型和8型金黄色葡萄球菌荚膜多糖与无毒重组铜绿假单胞菌外毒素A结合的疫苗的安全性、免疫原性和有效性，该试验纳入了接受血液透析的终末期肾病患者。在1998年4月至1999年8月期间，73个血液透析中心的1804名成年患者被随机分配，接受单次肌肉注射疫苗或生理盐水。对5型和8型金黄色葡萄球菌荚膜多糖的IgG抗体进行了长达两年的检测，并记录了金黄色葡萄球菌菌血症的发作情况。通过比较接受疫苗的患者与对照患者中金黄色葡萄球菌菌血症的发生率来评估疫苗的有效性。

结果

对疫苗的反应通常为轻度至中度，大多数在两天内消退。荚膜多糖在80%的5型患者和75%的8型患者中引发了至少每毫升80微克（估计的最低保护水平）的抗体反应。第3至54周期间的有效性仅为26%（P=0.23）。然而，在接种疫苗后的第3至40周之间，在892名可评估菌血症的疫苗组患者中，有11例发生了金黄色葡萄球菌菌血症，而对照组的906名患者中有26例发生了菌血症（有效性估计为57%；95%置信区间为10%至81%；名义P=0.02）。