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利用 LAE 技術開發抗綠膿桿菌感染疫苗

利用 LAE 技術開發抗綠膿桿菌感染疫苗.

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利用 LAE 技術開發抗綠膿桿菌感染疫苗

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  1. 利用LAE技術開發抗綠膿桿菌感染疫苗 • 綠膿桿菌（Pseudomonas aeruginosa）為革蘭氏陰性短桿菌，在自然界中廣泛分佈，對養分的需求少、生存條件極低，為最主要的院內感染（nosocomial infection） 伺機性感染病原菌（opportunistic infection pathogen）； 但此菌極易產生抗藥性引起治療上的困難，故急須開發疫苗來預防、治療綠膿桿菌感染，以取代傳統的抗生素療法。由於綠膿桿菌會分泌多種有毒物質，其中又以綠膿桿菌外毒素A（PE）之毒性最強，會進入血流中引起菌毒血症（bacteremia），感染者的死亡率常高達70%；而根據之前的研究結果顯示，如何有效的中和阻斷PE的毒性作用，並同時能抑制菌體本身的快速繁殖及侵犯組織，是對抗綠膿桿菌感染所迫切解決的問題。有鑑於此，本論文選取綠膿桿菌的外膜蛋白F（OprF）上的抗體辨認區段（F1,F2,F3,F4,F5）利用LAE（linear array epitope）的技術合成線性重複排列的抗體辨認區段，並融合PE的domain Ia作為抗原蛋白攜帶媒介（carrier），開發出新一代兩全其美的抗綠膿桿菌感染的疫苗PEDIa-Fn（n=1,2,4,5）。目前的實驗已證明，在BALB/cByJ小鼠及英格蘭雌兔的動物實驗中，此融合蛋白PEDIa-Fn（n=1,2,4,5）所誘發出的抗體不但能專一性的識別各種不同血清型綠膿桿菌的OprF，且能與菌體表面結合，進而促進巨噬細胞對菌體的調理吞噬作用，能有效對抗綠膿桿菌的快速繁殖及其對組織的侵犯，雙管齊下，達到較佳的免疫效果，因此可預期本疫苗為一種更有效的新型抗綠膿桿菌感染疫苗。

  2. Development of Linear Array Epitope (LAE) Vaccine against Pseudomonas aeruginosa Infection • Pseudomonas aeruginosa is an opportunistic pathogen that has become a major cause of nosocomial infections, and its well-known antibiotic resistance hinders therapy for P. aeruginosa infection; thus, there is considerable interest in the development of immunotherapy through either passive or active immunization. The most potent cytotoxic agent produced by P. aeruginosa is Pseudomonas exotoxin A (PE). In previous study, we know that most of P. aeruginosa infections are invasive and toxinogenic; therefore, we have designed a potent linear array epitopes (LAE) vaccine, the chimeric protein PEDIa-Fn( n=1,2,3,4,5 ), containing the receptor binding domain of PE (PE Domain Ia；PEDIa) and a linear array epitope of single motif of the outer membrane protein F (OprF) of P. aeruginosa.The potential of PEDIa-Fn（n=1,2,4,5）as a vaccine against P. aeruginosa infection is evaluated in BALB/cByJ mice and New Zealand white rabbits. At the present time, we have finished the examination of the titers of anti-PEDIa and anti-OprFFL antibodies. In addition, we have also demonstrated that the antibodies induced by chimeric protein PEDIa-F1-17 and PEDIa-F4-12 could not only recognize the OprF of various strains of P. aeruginosa but also promote the opsonophagocytic uptake of P. aeruginosa strain CCRC12902 by murine or rabbit peritoneal macrophages to prevent the colonization.

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