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分子生物学对铜绿假单胞菌免疫的影响。

Impact of molecular biology on Pseudomonas aeruginosa immunization.

作者信息

Pennington J E

机构信息

Department of Medicine, University of California San Francisco 94143.

出版信息

J Hosp Infect. 1988 Feb;11 Suppl A:96-102. doi: 10.1016/0195-6701(88)90173-9.

Abstract

Persisting high mortalities from Pseudomonas aeruginosa infection have led to new strategies for treatment. In vitro and animal studies indicate that antibodies against P. aeruginosa antigens increase host defense against this infectious agent. The most effective immunogen is lipopolysaccharide (LPS) antigen; however, LPS vaccines are poorly tolerated. Furthermore, the LPS molecule does not lend itself well to production by genetic engineering. Pseudomonas aeruginosa protein antigens which might be amenable to recombinant DNA production are outer membrane proteins and exotoxin A, modified to decrease toxicity but maintain immunogenicity. Another strategy for immunization with anti-LPS P. aeruginosa antibodies is passive administration of either hyperimmune immunoglobulins (polyclonal) or monoclonal antibodies. Passive immunization offers the dual advantage of rapid protection or treatment and is well tolerated. Several monoclonal antibodies against LPS P. aeruginosa antigens have been described, including both murine and human types. Studies in animal models of infection indicate that P. aeruginosa monoclonal antibodies do protect, thus, the most feasible application of molecular biology to the problem of P. aeruginosa infection appears to be production of immunotype-specific monoclonal antibodies for immune therapy.

摘要

铜绿假单胞菌感染导致的持续高死亡率促使人们探索新的治疗策略。体外和动物研究表明,抗铜绿假单胞菌抗原的抗体可增强宿主对这种感染因子的防御能力。最有效的免疫原是脂多糖(LPS)抗原;然而,LPS疫苗的耐受性较差。此外,LPS分子不太适合通过基因工程生产。可能适合重组DNA生产的铜绿假单胞菌蛋白抗原是外膜蛋白和外毒素A,经过修饰以降低毒性但保持免疫原性。用抗LPS铜绿假单胞菌抗体进行免疫的另一种策略是被动给予超免疫球蛋白(多克隆)或单克隆抗体。被动免疫具有快速提供保护或治疗的双重优势,且耐受性良好。已经描述了几种针对LPS铜绿假单胞菌抗原的单克隆抗体,包括鼠源和人源类型。感染动物模型的研究表明,铜绿假单胞菌单克隆抗体确实具有保护作用,因此,将分子生物学应用于铜绿假单胞菌感染问题最可行的方法似乎是生产用于免疫治疗的免疫型特异性单克隆抗体。

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