重组单链抗独特型抗体对新型隐球菌β-1,3-葡聚糖合酶及细胞生长的抑制作用

Inhibition of beta-1,3-glucan synthase and cell growth of Cryptococcus species by recombinant single-chain anti-idiotypic antibodies.

作者信息

Selvakumar Dakshnamurthy, Miyamoto Masahiko, Furuichi Yasuhiro, Komiyama Tadazumi

机构信息

Department of Biochemistry, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 5-13-2 Kamishinei-cho, Niigata 950-2081, Japan.

出版信息

J Antibiot (Tokyo). 2006 Feb;59(2):73-9. doi: 10.1038/ja.2006.10.

DOI:10.1038/ja.2006.10

PMID:16629406

Abstract

Recombinant single-chain fragment variable (scFv) anti-idiotypic antibodies were produced to represent the internal image of a HM-1 killer toxin, which is characterized by a wide spectrum of anti-fungal activity through inhibiting beta-1,3-glucan synthase (GS). We examined if scFv antibodies are active against Cryptococcus species, a human pathogen of increasing medical importance. The anti-cryptococcal activity of scFv antibodies and HM-1 were assessed by MIC analysis for C. neoformans IFM 40215 and C. albidus NBRC 0612 cells. The scFv antibodies had strong anti-cryptococcal activity in vitro with IC50 at 1.07 x 10(-7) to 2.60 x 10(-7) M for C. neoformans and C. albidus. Furthermore, the scFv antibodies potentially inhibited GS of C. neoformans with IC50 at 1.27 x 10(-7) to 2.27 x 10(-7) M. Both the anti-fungal and anti-GS activities of the scFv antibodies were markedly neutralized by the monoclonal antibody that neutralizes HM-1 killer toxin.

摘要

产生了重组单链可变片段（scFv）抗独特型抗体，以代表HM-1杀伤毒素的内影像，该毒素的特征是通过抑制β-1,3-葡聚糖合酶（GS）具有广泛的抗真菌活性。我们研究了scFv抗体是否对新型隐球菌具有活性，新型隐球菌是一种医学重要性日益增加的人类病原体。通过对新型隐球菌IFM 40215和浅白隐球菌NBRC 0612细胞进行MIC分析，评估了scFv抗体和HM-1的抗隐球菌活性。scFv抗体在体外对新型隐球菌和浅白隐球菌具有很强的抗隐球菌活性，对新型隐球菌和浅白隐球菌的IC50为1.07×10（-7）至2.60×10（-7）M。此外，scFv抗体对新型隐球菌的GS具有潜在抑制作用，IC50为1.27×10（-7）至2.27×10（-7）M。scFv抗体的抗真菌和抗GS活性均被中和HM-1杀伤毒素的单克隆抗体显著中和。