CONJUGATE-INDUCED POLYSACCHARIDE ANTIBODIES

革兰氏阴性肠道病原菌的表面多糖，以被膜或脂多糖的形式存在，既是重要的毒力因子，又是保护性抗原。通过与载体蛋白的结合，这些多糖的功效潜力得到了增强。在伤寒和其他肠道发热发病率较高的越南，成人(第1期)和儿童(第2期)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Vi结合物可引发针对伤寒的高增强应答。在第三阶段试验中，大约12,000名2-5岁儿童注射了结合疫苗，没有出现明显的副作用。甲型副伤寒沙门氏菌是东南亚第二常见的肠道热病因，在成人、青少年和2-4岁的儿童中被发现是安全的和免疫原性的。大肠杆菌O157是一种新出现的病原体，会导致幼儿溶血性尿毒症综合征。O157O特异性多糖-REPA结合物在成年志愿者中的第一阶段研究证明了其安全性和免疫原性。计划在2-5岁儿童中进行第二阶段研究。从突变的E.ColiO157中提纯无毒志贺毒素I，并将其与O-特异性多糖偶联制成双价疫苗。O157大肠杆菌的主要宿主是牛。脂多糖和O-特异性多糖结合物在牛身上显示出免疫原性，并计划进行一项攻击性研究，以证明牛体内携带状态的清除。霍乱弧菌O1和O139是霍乱感染的主要血清型。用O-特异性多糖合成的偶联物在小鼠体内诱导产生杀弧菌抗体。这些结合物的临床试验正在计划中。-人类科目

Surface polysaccharides of Gram-negative enteric pathogens, in the form of capsule or lipopolysaccharide, are both essential virulence factors and protective antigens. The potential for efficacy of these polysaccharide was enhanced by binding to carrier proteins. Sequential clinical studies in adults (phase 1) and in children (phase 2) in Vietnam, an area with a high attack rate of typhoid and other enteric fevers, showed that Vi conjugates bound to the recombinant Pseudomonas aeruginosa exoprotein A (rEPA) elicited high booster responses against typhi. In phase 3 trial, About 12,000 2-5 years old children injected with the conjugate vaccine showed no significant side reaction. 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 O-specific polysaccharide elicited vibriocidal antibodies in mice. Clinical trials of these conjugates are planned. - Human Subjects