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恶性疟原虫环子孢子蛋白C端片段:临床前评估与I期临床研究

Plasmodium falciparum CS C-terminal fragment: preclinical evaluation and phase I clinical studies.

作者信息

Roggero M A, Weilenmann C, Bonelo A, Audran R, Renggli J, Spertini F, Corradin G, López J A

机构信息

Institut de Biochimie, Université de Lausanne, Switzerland.

出版信息

Parassitologia. 1999 Sep;41(1-3):421-4.

PMID:10697896
Abstract

Preclinical evaluation of synthetic peptides corresponding to the C-terminal regions of the circumsporozoite (CS) protein in various Plasmodia showed that these preparations were immunogenic and safe upon injection in various animal models. Additionally, the corresponding peptide from Plasmodium falciparum was widely recognized by sera and PBL obtained from semi-immune adults living in malaria endemic areas. Moreover, the CS C-terminal peptide derived from P. berghei conferred protection upon challenge with live sporozoites in mice. A GLP preparation of the synthetic peptide corresponding to residues 282-383 of the Pf CS, NF-54 strain is currently evaluated in a open, non-randomized, Phase I human trial. Data obtained after the second antigen injection show that the malaria vaccine Pf CS 282-383 is safe, well tolerated and gives rise to high antibody titre, CD4+ and CD8+ lymphocyte responses.

摘要

对各种疟原虫中与环子孢子(CS)蛋白C端区域相对应的合成肽进行的临床前评估表明,这些制剂在注射到各种动物模型中时具有免疫原性且安全。此外,来自生活在疟疾流行地区的半免疫成年人的血清和外周血淋巴细胞(PBL)广泛识别来自恶性疟原虫的相应肽。此外,源自伯氏疟原虫的CS C端肽在小鼠受到活子孢子攻击时提供了保护。目前正在一项开放、非随机的I期人体试验中评估对应于Pf CS NF-54株282-383位残基的合成肽的GLP制剂。第二次抗原注射后获得的数据表明,疟疾疫苗Pf CS 282-383是安全的,耐受性良好,并能引起高抗体滴度、CD4 +和CD8 +淋巴细胞反应。

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