宋内志贺菌-CRM9与福氏2a型志贺菌-rEPA琥珀酸共轭疫苗在1至4岁儿童中的安全性和免疫原性。

Safety and immunogenicity of Shigella sonnei-CRM9 and Shigella flexneri type 2a-rEPAsucc conjugate vaccines in one- to four-year-old children.

作者信息

Passwell Justen H, Ashkenazi Shai, Harlev Efrat, Miron Dan, Ramon Reut, Farzam Nahid, Lerner-Geva Liat, Levi Yonit, Chu Chiayung, Shiloach Joseph, Robbins John B, Schneerson Rachel

机构信息

Samuel Jared Kushnick Immunology Laboratory, Safra Childrens Hospital, Sheba Medical Center, Tel Hashomer, Israel 52621.

出版信息

Pediatr Infect Dis J. 2003 Aug;22(8):701-6. doi: 10.1097/01.inf.0000078156.03697.a5.

DOI:10.1097/01.inf.0000078156.03697.a5

PMID:12913770

Abstract

BACKGROUND AND OBJECTIVE

Shigella conjugate vaccines have been shown to be safe, immunogenic and efficacious in adult volunteers. We have now investigated the safety and immunogenicity of investigational Shigella sonnei and Shigella flexneri 2a conjugate vaccines in 1- to 4-year-old children, the age group at greatest risk for shigellosis.

METHODS

The O-specific polysaccharides of S. sonnei and S. flexneri 2a, the two most common shigellae from patients in Israel, were bound to medically useful carrier proteins to form conjugates. Eighty healthy 1- to 4-year-olds were randomized to receive two 0.5-ml im injections 6 weeks apart of either S. sonnei-CRM(9) or S. flexneri 2a-rEPA(succ). Blood was taken before, 6 weeks after the first injection, 4 weeks after the second injections and 2 years after immunization for assay of IgG anti-lipopolysaccharide, diphtheria toxin and Pseudomonas aeruginosa exotoxin A antibodies by enzyme-linked immunosorbent assay.

RESULTS

During an 8-day surveillance period after each immunization, low fever (37.8-39.0 degrees C) lasting only 24 to 48 h occurred in 2 of 40 recipients after the first injection and 4 of 40 recipients after the second injection of S. flexneri 2a-rEPA(succ) and in 2 of 38 of S. sonnei-CRM(9) after the second injection; no fever was detected after the first injection. Liver function tests were normal in all vaccinees. S. sonnei-CRM(9) elicited a >4-fold rise in IgG anti-LPS in 92.1% and S. flexneri 2a-rEPA(succ) in 85% (P < 0.0001) after the second injection; both conjugates elicited type-specific booster responses. At 2 years the geometric mean concentrations of both IgG anti-lipopolysaccharides were significantly higher than preimmunization levels. A >4-fold rise of IgG anti-diphtheria (65.8%) and IgG anti-ETA (77.5%) was observed.

CONCLUSION

These experimental Shigella conjugate vaccines were safe and immunogenic in 1- to 4-year-old children.

摘要

背景与目的

志贺氏菌结合疫苗已在成年志愿者中显示出安全性、免疫原性和有效性。我们现在研究了试验性宋内志贺氏菌和福氏志贺氏菌2a结合疫苗在1至4岁儿童中的安全性和免疫原性，这一年龄组是志贺氏菌病风险最高的群体。

方法

将以色列患者中最常见的两种志贺氏菌——宋内志贺氏菌和福氏志贺氏菌2a的O特异性多糖与医用载体蛋白结合形成结合物。80名健康的1至4岁儿童被随机分为两组，分别在6周内间隔注射两次0.5毫升的宋内志贺氏菌-CRM(9)或福氏志贺氏菌2a-rEPA(琥珀酸)。在首次注射前、首次注射后6周、第二次注射后4周以及免疫后2年采集血液，通过酶联免疫吸附测定法检测IgG抗脂多糖、白喉毒素和铜绿假单胞菌外毒素A抗体。

结果

在每次免疫后的8天监测期内，首次注射福氏志贺氏菌2a-rEPA(琥珀酸)后，40名接种者中有2人出现持续仅24至48小时的低热(37.8-39.0摄氏度)，第二次注射后有4人出现；第二次注射宋内志贺氏菌-CRM(9)的38名接种者中有2人出现低热；首次注射后未检测到发热。所有接种疫苗者的肝功能测试均正常。第二次注射后，宋内志贺氏菌-CRM(9)使92.1%的接种者IgG抗LPS升高超过4倍，福氏志贺氏菌2a-rEPA(琥珀酸)使85%的接种者升高超过4倍(P < 0.0001)；两种结合物均引发了型特异性加强反应。在2年时，两种IgG抗脂多糖的几何平均浓度均显著高于免疫前水平。观察到IgG抗白喉(65.8%)和IgG抗ETA(77.5%)升高超过4倍。