Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1-4-year-old Israeli children
Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1-4-year-old Israeli children
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DOI：
10.1016/j.vaccine.2009.12.050
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发表时间：
2010-03-02
期刊：
影响因子：
5.5
通讯作者：
Schneerson, Rachel
中科院分区：
文献类型：
--
作者：
Passwell, Justen H.;Ashkenzi, Shai;Schneerson, Rachel
背景：尽管志贺氏菌病在世界范围内发病率和死亡率很高，但目前还没有获得批准的志贺氏菌病疫苗。我们报道了宋内氏志贺氏菌O-特异性多糖-蛋白结合物在成人和幼儿中的安全性和免疫原性以及在青壮年的效果。方法：对宋内氏志贺菌和福氏2a志贺氏菌O-SP-REPA结合物进行双盲、随机和疫苗对照的第三阶段评价，25 mU LG两次注射，相隔6周，对健康1-4岁儿童进行免疫接种。每隔一周通过电话对这些儿童进行为期两年的跟踪调查，并对每次急性腹泻(每天3次大便松弛或1次血性/粘液性大便)进行大便培养。结果：2799名入选者中，1433人接种了宋内氏志贺氏菌和1366株福氏2a志贺菌，2699人(96.4%)完成2年随访。局部反应发生在类似于5%和类似于4%的情况下，温度为-38.0℃，持续1-2天。没有出现与疫苗有关的严重不良事件。在获得的3295个粪便培养物中，125个产生宋内氏链球菌，21个产生福氏2a志贺氏菌。免疫原性和疗效与年龄有关。3~4岁儿童的总有效率分别为27.5%和71.1%(P=0.043)。福氏2a志贺氏菌的数量太少，无法进行有意义的分析。福氏2a志贺氏菌对非疫苗福氏志贺氏菌有交叉保护作用，但数量太少，没有统计学意义。两组疫苗特异性免疫球蛋白抗体水平均随年龄增长而升高，在接种后10周左右达到高峰，此后下降，但在第二次接种后2年仍高于对照组的4倍。结论：志贺氏菌结合物在1~4岁儿童是安全和免疫原性的。松内沙门氏菌结合物在3-4岁儿童中的有效率为71.1%，可以预测在3岁以上的儿童中有效。这些结果促使人们研究我们改进的偶联物。爱思唯尔有限公司出版。
Background: Despite its high worldwide morbidity and mortality, there is yet no licensed vaccine for shigellosis. We reported the safety and immunogenicity of Shigella O-specific polysaccharide-protein conjugates in adults and young children and efficacy ofShigella sonnei conjugate in young adults.Methods: A double-blinded, randomized and vaccine-controlled Phase3 evaluation of S. sonnei and Shigella flexneri 2a O-SP-rEPA conjugates, 25 mu Lg, injected IM twice, 6 weeks apart, into healthy 1 -4 years old, is reported. The children were followed for 2 years by telephone every other week and stool cultures were obtained for each episode of acute diarrhea (>= 3 loose stools/day or a bloody/mucous stool). Sera were taken randomly from 10% of the participants for IgG anti-LPS and anti-carrier levels.Results: Of the 2799 enrollees, 1433 received S. sonnei and 1366 S. flexneri 2a conjugates; 2699 (96.4%) completed the 2-year follow-up. Local reactions occurred in similar to 5% and similar to 4% had temperatures >= 38.0 degrees C lasting 1-2 days. There were no serious adverse events attributable to the vaccines. Of the 3295 stool cultures obtained, 125 yielded S. sonnei and 21 S. flexneri 2a. Immunogenicity and efficacy were age-related. The overall efficacy of the S. sonnei conjugate was 27.5%; 71.1% (P= 0.043) in the 3-4 years old. The numbers for S.flexneri 2a were too few for meaningful analysis. Cross-protection by S.flexneri 2a for non-vaccine S. flextierl types was found, but the numbers were too few for statistical significance. There was an age-related rise of vaccine-specific IgG anti-LPS in both groups, peaking at about 10 weeks and declining thereafter, but remaining >= 4-fold higher than in the controls 2 years after the second dose.Conclusions: Shigella conjugates are safe and immunogenic in 1-4 years old. The S. sonnei conjugate elicited 71.1% efficacy in the 3-4 years old and can be predicted to be efficacious in individuals older than 3 years of age. These results urge studies with our improved conjugates. Published by Elsevier Ltd.