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铜绿假单胞菌外膜蛋白作为候选疫苗

Outer membrane proteins of Pseudomonas aeruginosa as vaccine candidates.

作者信息

von Specht B U, Domdey H, Schödel F, Blum B, Lücking C, Knapp B, Muth G, Hungerer K D, Bröker M

机构信息

Chirurgische Universitäs-Klinik Freiburg, Germany.

出版信息

Behring Inst Mitt. 1994 Dec(95):85-96.

PMID:7538752
Abstract

We tested the ability of recombinant outer membrane proteins of Pseudomonas aeruginosa to serve as a protective vaccine against this gram negative pathogen under two main pathophysiological events leading to P. aeruginosa sepsis. i) systemic infection during immunosuppression, and ii) bacterial translocation. A hybrid vaccine was cloned combining protective epitopes of outer membrane protein F (OprF) and outer membrane protein I (OprI). This vaccine proved to be highly protective against an intraperitoneal challenge with P. aeruginosa in immunosuppressed mice. Oral immunization of mice, with recombinant Salmonella dublin expressing OprI induced s-IgA antibodies in the gut mucosa against OprI and provided protection against translocation of P. aeruginosa in an immunosuppressed mouse model. To test whether OprI is safe for use in humans, recombinant OprI was purified and used for immunization of volunteers. Vaccination was well tolerated and no major side effects were observed. The induction of serum antibodies against OprI was found to be dose-dependent and was observed in total in 65% of the volunteers.

摘要

我们测试了铜绿假单胞菌重组外膜蛋白在导致铜绿假单胞菌败血症的两种主要病理生理事件下作为针对这种革兰氏阴性病原体的保护性疫苗的能力。i)免疫抑制期间的全身感染,以及ii)细菌移位。克隆了一种混合疫苗,其结合了外膜蛋白F(OprF)和外膜蛋白I(OprI)的保护性表位。该疫苗在免疫抑制小鼠中被证明对铜绿假单胞菌的腹腔攻击具有高度保护作用。用表达OprI的重组都柏林沙门氏菌对小鼠进行口服免疫,可在肠道黏膜中诱导针对OprI的分泌型IgA抗体,并在免疫抑制小鼠模型中提供针对铜绿假单胞菌移位的保护作用。为了测试OprI用于人类是否安全,纯化了重组OprI并用于志愿者免疫。疫苗接种耐受性良好,未观察到重大副作用。发现针对OprI的血清抗体诱导呈剂量依赖性,总共在65%的志愿者中观察到。

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