Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2-to 4-year-old children in Vietnam
Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2-to 4-year-old children in Vietnam
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DOI：
10.1128/iai.67.11.5806-5810.1999
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发表时间：
1999-11-01
影响因子：
3.1
通讯作者：
Szu, SC
中科院分区：
文献类型：
--
作者：
Kossaczka, Z;Lin, FYC;Szu, SC
伤寒沙门氏菌的荚膜多糖Vi是一种重要的毒力因子，也是5岁以上人群的保护性疫苗。在越南成人、5- 14岁儿童和2- 4岁儿童中评价了两种研究性Vi结合疫苗的安全性和免疫原性。以铜绿假单胞菌重组胞外蛋白A（rEPA）作为载体，使用N-琥珀酰亚胺基-3-（2-吡啶二硫基）-丙酸酯（SPDP; Vi-rEPA（1））或己二酸二酰肼（ADN; Vi-rEPA（2））作为接头制备缀合物。所有接受者的体温均未超过38.5摄氏度或出现明显的局部反应。向成人注射一次Vi-rEPA（2）后，抗Vi免疫球蛋白G（IgG）的几何平均值（GM）从9. 62酶联免疫吸附测定单位/ml（EU）增加至6周时的465 EU; 26周后该水平降至119 EU。在5至14岁儿童中，Vi-rEPA（2）、Vi-rEPA（1）和Vi在6周时引起的抗Vi IgG水平分别为169、22.8和18.9 EU（Vi-rEPA（1）和Vi相对于Vi-rEPA（2）的P = 0.0001）。在26周时，Vi-rEPA（2）、Vi-rEPA（1）和Vi接受者的抗Vi IgG水平分别为30.0、10.8和13.4 EU（Vi-rEPA（1）和Vi相对于Vi-rEPA（2）的P < 0.001）;均高于注射前水平（P = 0.0001）。Vi-REPA（2）也引起三种疫苗中最高的抗Vi IgM和伊加水平。在首次注射后6周的2至4岁儿童中，Vi-rEPA（2）引起的抗Vi IgG水平为69.9 EU，而Vi-rEPA（1）为28.9 EU（P = 0.0001）。再次注射使Vi-rEPA的Vi抗体水平从69.9 EU增加至95.4 EU（2），Vi-rEPA的Vi抗体水平从28.9 EU增加至83.0 EU（1）。在26周时，抗Vi IgG水平仍高于注射前水平（Vi-rEPA（2）为30.6 vs 0.18，Vi-rEPA（1）为12.8 vs 0.33;两者P = 0.0001）。建议5岁或以上的人接种Vi疫苗。在本研究中，在2至4岁儿童中通过两次注射Vi-rEPA（2）引起的抗Vi IgG elf的GM水平高于在5至14岁儿童中通过Vi引起的GM水平（30.6 vs 13.4; P = 0.0001）。Vi-rEPA（2）结合物的安全性和免疫原性需要进一步研究。
The capsular polysaccharide of Salmonella typhi, Vi, is an essential virulence factor and a protective vaccine for people older than 5 years. The safety and immunogenicity of two investigational Vi conjugate vaccines were evaluated in adults, 5- to 14-year-old children, and 2- to 4-year-old children in Vietnam. The conjugates were prepared with Pseudomonas aeruginosa recombinant exoprotein A (rEPA) as the carrier, using either N-succinimidyl-3-(2-pyridyidithio)-propionate (SPDP; Vi-rEPA(1)) or adipic acid dihydrazide (ADN; Vi-rEPA(2)) as linkers. None of the recipients experienced a temperature of >38.5 degrees C or significant local reactions. One injection of Vi-rEPA(2) into adults elicited a geometric mean (GM) increase in anti-Vi immunoglobulin G (IgG) from 9.62 enzyme-linked immunosorbent assay units/ml (EU) to 465 EU at 6 weeks; this level fell to 119 EU after 26 weeks. In the 5- to 14-year-old children, anti-Vi IgG levels at 6 weeks elicited by Vi-rEPA(2), Vi-rEPA(1), and Vi were 169, 22.8, and 18.9 EU, respectively (P = 0.0001 for Vi-rEPA(1) and Vi with respect to Vi-rEPA(2)). At 26 weeks, the anti-Vi IgG levels for recipients of Vi-rEPA(2), Vi-rEPA(1), and Vi were 30.0, 10.8, and 13.4 EU, respectively (P < 0.001 for Vi-rEPA(1) and Vi with respect to Vi-rEPA(2)); all were higher than the preinjection levels (P = 0.0001). Vi-REPA(2) also elicited the highest anti-Vi IgM and IgA levels of the three vaccines. In the 2- to 4-year-old children at 6 weeks following the first injection, Vi-rEPA(2) elicited an anti-Vi IgG level of 69.9 EU compared to 28.9 EU for Vi-rEPA(1) (P = 0.0001). Reinjection increased Vi antibody levels from 69.9 to 95.4 EU for Vi-rEPA(2) and from 28.9 to 83.0 EU for Vi-rEPA(1). At 26 weeks, anti-Vi IgG levels remained higher than those at preinjection (30.6 versus 0.18 for Vi-rEPA(2) and 12.8 versus 0.33 for Vi-rEPA(1); P = 0.0001 for both). Vi vaccine is recommended for individuals of 5 years of age or older. In the present study, the GM level of anti-Vi IgG elf cited by two injections of Vi-rEPA(2) in the 2- to 4-year-old children was higher than that elicited by Vi in the 5- to 14-year-old children (30.6 versus 13.4; P = 0.0001). The safety and immunogenicity of the Vi-rEPA(2) conjugate warrant further investigation.