Immunogenicity of multivalent Shigella-ETEC candidate vaccine strains in a guinea pig model
Immunogenicity of multivalent Shigella-ETEC candidate vaccine strains in a guinea pig model
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DOI：
10.1016/j.vaccine.2005.07.013
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发表时间：
2006-05-01
期刊：
影响因子：
5.5
通讯作者：
Levine, Myron M.
中科院分区：
文献类型：
--
作者：
Barry, Eileen M.;Wang, Jin;Levine, Myron M.
志贺氏菌属和产肠毒素大肠杆菌仍然是发展中国家婴幼儿腹泻的重要原因，也是旅行者腹泻的流行因素。一种疫苗，提供保护，防止疾病引起的两种病原体将服务于共同的风险人群。这样的疫苗需要包含多种志贺氏菌菌株以及多种ETEC抗原。使用志贺氏菌减毒株作为表达ETEC抗原的活载体是开发这种多价疫苗的一种策略。S. flexneri 2a，S. sonnei和S.构建了含有guaBA生物合成途径基因以及编码肠毒素的基因缺失的Aperteriae 1。随后将每种菌株用作表达一种或两种关键ETEC抗原的活载体。在豚鼠模型中测试所得的三种志贺氏菌衍生菌株单独或作为混合物的免疫原性和保护能力。S.福氏志贺菌CVD 1208（pCFA/I-CS3）、志贺菌S. flexneri菌株CVD 1208（pCFA/I-CS3）、S. flexneri菌株CVD 1208（pCFA/I-CS3）、S. flexneri菌株CVD 1208（pCFA/I-CS3）。Sonnei菌株CVD 1233（pCS 4-LThK 63）和S.大肠杆菌1菌株CVD 1252（pCS 2）能够引发针对活载体以及客体ETEC抗原的血清和粘膜抗体应答。使用这些菌株中的两种或三种的组合进行疫苗接种能够引发针对每种活载体以及混合物中代表的每种ETEC抗en的特异性免疫应答。这些研究证明了使用表达ETEC抗原的活志贺氏菌衍生物的混合物作为免疫原性多价疫苗的潜力。(c)2005爱思唯尔有限公司保留所有权利。
Shigella and enterotoxigenic Escherichia coli continue to be significant causes of diarrheal disease in infants and young children in developing countries as well as prevalent agents of traveler's diarrhea. A vaccine which provides protection against disease caused by both pathogens would serve common at-risk populations. Such a vaccine would require inclusion of multiple Shigella strains as well as multiple ETEC antigens. The use of attenuated strains of Shigella as live vectors for the expression of ETEC antigens is one strategy for the development of such a multivalent vaccine. Live attenuated strains of S. flexneri 2a, S. sonnei and S. dysenteriae 1 containing deletions in guaBA biosynthetic pathway genes as well as in genes encoding enterotoxins, were constructed. Each strain was subsequently used as a live vector for the expression of one or two critical ETEC antigens. The resulting three Shigella derivative strains were tested for immunogenicty and protective capacity alone or as mixtures in the guinea pig model. S. flexneri strain CVD 1208(pCFA/I-CS3), S. sonnei strain CVD 1233(pCS4-LThK63) and S. dysenteriae 1 strain CVD 1252(pCS2) were able to elicit serum and mucosal antibody responses against the live vector as well as the guest ETEC antigens. Vaccination with combinations of two or three of these strains was able to elicit specific immune responses against each live vector as well as each ETEC anti-en represented in the mixture. These studies demonstrate the potential of the use of mixtures of live Shigella derivatives expressing ETEC antigens to serve as an immunogenic multivalent vaccine. (c) 2005 Elsevier Ltd. All rights reserved.