CAPSULAR POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES OF VIBRIO VULNIFICUS

创伤弧菌荚膜多糖-蛋白结合疫苗

• 批准号: 5200680
• 负责人: S DEVI
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200680
• 关键词: Vibrio; active immunization; antibacterial antibody; antiserum; bacterial capsules; bacterial polysaccharides; bacterial vaccines; hyperimmunization; immunoconjugates; laboratory mouse; nonhuman therapy evaluation; passive immunization; tetanus toxoid

Vibrio vulnificus causes fatal septicemic and wound infections in immunocompromised and normal humans. The capsular polysaccharide of V. vulnificus (VvPS) is critical for virulence. Previously, we developed a variety of conjugate vaccines by conjugating VvPS to tetanus toxoid (TT), and cytolysin and elastase of V. vulnificus and evaluated their protective efficacy following active immunization. We have now evaluated the immunoprophylactic and immunotherapeutic efficacy of murine and rabbit hyperimmune antisera, prepared using VvPS-TTa and VvPS-TTb conjugates, in a murine model. Total protection (100%) was conferred by VvPS-TT conjugate-induced antisera when administered 24 hours before lethal challenge with homologous carbotype of V. Vulnificus, and 60-73% protection was observed in mice which were treated with the antisera 2 hours after lethal infection, at a stage when the symptoms of sickness were quite apparent. There was 67-100% mortality among control mice injected with normal serum or with antisera to irrelevant polysaccharides or proteins. This reversal of disease course elicited by conjugate-induced antisera is most relevant to a human setting, particularly in patients who get admitted with advanced infection with a very short window of time available to the physicians to treat. Given the high mortality rate in humans of 55-79% despite aggressive antibiotic and supportive therapy, and the rapid progression of septicemia to death (24-48 h), the results of passive protection experiments become highly significant and clinically relevant. The results suggest the feasibility of using VvPS conjugate-induced hyper immune globulins in the immunoprophylaxis of high risk populations and immunotherapy in the clinical management of patients with V. vulnificus septicemia.

创伤弧菌可导致致命的败血症和伤口感染， 免疫功能低下的人和正常人。 V. 创伤弧菌（VvPS）的毒力至关重要。 此前，我们开发了 通过将VvPS与破伤风类毒素缀合而制备的多种缀合疫苗 (TT)和弹性蛋白酶，并评价了它们在创伤弧菌中的作用。 主动免疫后的保护效果。 我们现在已经评估了 小鼠和 使用VvPS-TTa和VvPS-TTb制备的兔超免疫抗血清 缀合物，在鼠模型中。 全面保护（100%）由 VvPS-TT缀合物诱导的抗血清，在24小时前给药 用创伤弧菌同源碳型攻击致死，60-73% 在用抗血清2处理的小鼠中观察到保护作用 致命感染后数小时，在疾病症状出现的阶段， 很明显 对照组小鼠的死亡率为67-100% 注射正常血清或不相关多糖的抗血清 或蛋白质。 这种逆转的疾病过程引起的， 缀合物诱导的抗血清与人类环境最相关， 尤其是那些晚期感染的病人， 一个非常短的时间窗口可供医生治疗。鉴于 尽管使用了积极的抗生素， 和支持性治疗，以及败血症的快速发展至死亡 （24-48 h），被动保护实验结果变得高度 显著且临床相关。 结果表明， 使用VvPS缀合物诱导的超免疫球蛋白， 高危人群的免疫预防和免疫治疗 创伤弧菌败血症患者的临床管理。