CONJUGATE-INDUCED POLYSACCHARIDE ANTIBODIES

革兰氏阴性肠道病原菌的表面多糖以胶囊或脂多糖的形式存在，是必不可少的毒力因子和保护性抗原。多糖的免疫原性通过与载体蛋白的结合而增强。在伤寒高发地区越南的成人和儿童的连续临床研究表明，与重组铜绿假单胞菌外蛋白a （rEPA）结合的荚膜多糖（Vi）偶联物引起了对伤寒的高反应。在一项III期试验中，约12,000名2-5岁儿童注射了这种结合疫苗，没有出现明显的副作用。主动监测27个月后，Vi-rEPA的有效率为91%。甲型副伤寒沙门氏菌是东南亚地区引起肠热的第二大常见原因，在成人、青少年和2-4岁儿童中被发现是安全且具有免疫原性的。大肠杆菌O157是一种新出现的病原体，可引起幼儿溶血性尿毒症综合征。O157 o特异性多糖- repa偶联物在成人志愿者中的1期研究证明了安全性和免疫原性。计划在2-5岁儿童中进行第二阶段研究。无毒志贺毒素I是从突变型大肠杆菌O157中纯化出来的，并与o特异性多糖结合用于二价疫苗。O157大肠杆菌的主要宿主是牛。LPS和o特异性多糖缀合物在牛体内显示出免疫原性，计划进行一项挑战研究以证明在牛体内清除运输状态。霍乱弧菌O1和O139是霍乱感染的主要血清型。O139荚膜多糖合成的偶联物可在小鼠体内引发杀弧菌抗体。这些结合物的临床试验正在计划中。

Surface polysaccharides of Gram-negative enteric pathogens, in the form of capsule or lipopolysaccharide, are both essential virulence factors and protective antigens. The immunogenicity of these polysaccharide was enhanced by binding to carrier proteins. Sequential clinical studies in adults and in children in Vietnam, an area with a high attack rate of typhoid, showed that the capsular polysaccharide (Vi)conjugates bound to the recombinant Pseudomonas aeruginosa exoprotein A (rEPA) elicited high responses against typhi. In a Phase III trial, About 12,000 2-5 years old children injected with the conjugate vaccine showed no significant side reaction. The efficacy of Vi-rEPA was 91% after 27 months active surveillance. Salmonella paratyphi A, the second most common cause of enteric fever in Southeast Asia, were found to be safe and immunogenic in adults, teenagers and then 2-4 year old children. Escherichia coli O157, an emerging pathogen, causes hemolytic uremic syndrome in young children. Phase 1 study of O157 O-specific polysaccharide-rEPA conjugate demonstrated safety and immunogenicity in adult volunteers. A phase 2 study in children 2-5 year olds is planned. Non-toxic shiga toxin I are purified from mutant E. coli O157 and to be conjugated with O-specific polysaccharide for a bivalent vaccine. The major reservoir of E.coli O157 is cattle. LPS and O-specific polysaccharide conjugate showed to be immunogenic in cattle and a challenge study is planned to demonstrate the clearance of the carriage state in cattle. Vibrio cholera O1 and O139 are the major sero types in cholera infections. Conjugates synthesized with capsular polysaccharide of O139 elicited vibriocidal antibodies in mice. Clinical trials of these conjugates are planned.