Pierre P G, Lucas G, Van Damme M, Vaerman J P
UCL-ICP-MEXP, Brussels.
Acta Gastroenterol Belg. 1992 Sep-Dec;55(5-6):430-6.
Cholera disease remains an important cause of morbidity and mortality in the third world. The parenteral cholera vaccine actually used offers only a 50% protection during 6 months. As Vibrio cholerae and its toxin don't cross the gut wall, the aim of new vaccines is to prevent the colonization and growth of the vibrio in the jejuno-ileum and to inhibit the fixation of cholera toxin (CT) on its enterocyte membrane receptor. This can be afforded by stimulation of the gut local immune system mainly represented by secretory IgA antibodies (Abs). New vaccines should comprise both bacterial and CT antigens and must be given by the oral route to induce the production of specific secretory IgA Abs in the gut. Four different ways are actually under study to produce an oral cholera vaccine. 1. Combination of CT-B subunit and killed vibrios. 2. Live recombinant Vibrio cholerae in which the CT coding gene has been deleted. 3. Synthetic peptides reproducing some immunodominant CT-epitopes. 4. Manipulation of the idiotypic network to induce the production of Abs mimicking CT-epitopes. This paper reviews the actual developments and advantages of these four approaches.
霍乱病仍然是第三世界发病和死亡的一个重要原因。实际使用的注射用霍乱疫苗在6个月内仅提供50%的保护。由于霍乱弧菌及其毒素不会穿过肠壁,新疫苗的目标是防止弧菌在空肠回肠中定植和生长,并抑制霍乱毒素(CT)在其肠细胞膜受体上的结合。这可以通过刺激主要由分泌型IgA抗体(Abs)代表的肠道局部免疫系统来实现。新疫苗应包含细菌和CT抗原,并且必须通过口服途径给药,以诱导肠道中产生特异性分泌型IgA抗体。目前正在研究四种不同的方法来生产口服霍乱疫苗。1. CT-B亚基与灭活弧菌的组合。2. 缺失CT编码基因的活重组霍乱弧菌。3. 复制一些免疫显性CT表位的合成肽。4. 操纵独特型网络以诱导产生模拟CT表位的抗体。本文综述了这四种方法的实际进展和优势。