Fontaine A, Arondel J, Sansonetti P J
Unité de Pathogénie microbienne moléculaire, INSERM U199, Institut Pasteur, Paris.
Res Microbiol. 1990 Sep-Oct;141(7-8):907-12. doi: 10.1016/0923-2508(90)90129-e.
Shigellosis is an invasive disease of the human colon which is particularly prevalent among children of the developing world. No proper vaccine is available to protect against this enteric disease. It is currently accepted that only live strains with attenuated virulence administered orally may elicit protective immunity at the level of the colonic mucosa, which is the exclusive site of multiplication of causative microorganisms such as Shigella flexneri and Shigella dysenteriae 1. We have constructed such vaccine candidates based on the destruction of virulence genes responsible for selected steps of the infection process. In S. flexneri, a combination of two mutations impairing cell-to-cell spread (icsA) and aerobactin production and transport (iuc, iut) which support growth within tissues provide a well tolerated and protective vaccine prototype against shigellosis in macaque monkeys. In S. dysenteriae 1, similar mutations are currently being introduced, in addition to one which eliminates the catalytic activity of Shiga toxin. These mutants and others will be tested soon in human phase I trials.
志贺氏菌病是一种侵袭人类结肠的疾病，在发展中国家的儿童中尤为普遍。目前尚无有效的疫苗来预防这种肠道疾病。目前公认的是，只有口服减毒活菌株才能在结肠黏膜水平引发保护性免疫，而结肠黏膜是诸如福氏志贺氏菌和痢疾志贺氏菌1等致病微生物唯一的繁殖部位。我们通过破坏负责感染过程特定步骤的毒力基因构建了此类候选疫苗。在福氏志贺氏菌中，两种损害细胞间传播（icsA）以及支持组织内生长的气杆菌素产生和运输（iuc、iut）的突变组合，为猕猴提供了一种耐受性良好且具有保护性的志贺氏菌病疫苗原型。在痢疾志贺氏菌1中，除了一种消除志贺毒素催化活性的突变外，目前也正在引入类似的突变。这些突变体和其他突变体很快将在人体I期试验中进行测试。
