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用重组Pfs16痘苗病毒和/或酵母中产生的重组Pfs16蛋白进行疫苗接种后诱导恶性疟原虫子孢子中和抗体。

Induction of Plasmodium falciparum sporozoite-neutralizing antibodies upon vaccination with recombinant Pfs16 vaccinia virus and/or recombinant Pfs16 protein produced in yeast.

作者信息

Moelans I I, Cohen J, Marchand M, Molitor C, de Wilde P, van Pelt J F, Hollingdale M R, Roeffen W F, Eling W M, Atkinson C T

机构信息

Department of Molecular Biology, Faculty of Science, University of Nijmegen, The Netherlands.

出版信息

Mol Biochem Parasitol. 1995 Jun;72(1-2):179-92. doi: 10.1016/0166-6851(95)00072-9.

DOI:10.1016/0166-6851(95)00072-9
PMID:8538688
Abstract

Pfs16 is a sexual stage/sporozoite-specific antigen of Plasmodium falciparum and is a potential candidate for a sporozoite-neutralizing vaccine. To obtain more information on the function of Pfs16 and to investigate its role during transmission and hepatocyte invasion, immunization experiments were performed with both a Pfs16-specific recombinant vaccinia virus and virus-like particles produced in yeast composed of the hepatitis B surface antigen (HBsAg) and antigen Pfs16 fused to HBsAg. Upon transformation of yeast cells, harbouring a genomic copy of the HBsAg gene, with a plasmid carrying the fusion gene Pfs16-HBsAg (Pfs16-S) virus-like hybrid particles composed of HBsAg and Pfs16-S were formed of a size similar to those present in human sera after infection with the hepatitis B virus. Cells infected with recombinant Pfs16 vaccinia virus synthesized a polypeptide of approx. 16 kDa that reacted with a Pfs16-specific polyclonal antibody. Animals vaccinated with the yeast hybrid particles and/or recombinant vaccinia virus both produced Pfs16-specific antibodies. These antibodies showed no transmission-blocking activity, but they efficiently diminished or abolished in vitro invasion of sporozoites into human hepatoma cells (HepG2-A16) and primary human hepatocytes.

摘要

Pfs16是恶性疟原虫的一个有性阶段/子孢子特异性抗原,是子孢子中和疫苗的一个潜在候选物。为了获得更多关于Pfs16功能的信息,并研究其在传播和肝细胞入侵过程中的作用,使用Pfs16特异性重组痘苗病毒和在酵母中产生的由乙型肝炎表面抗原(HBsAg)和与HBsAg融合的抗原Pfs16组成的病毒样颗粒进行了免疫实验。在用携带融合基因Pfs16-HBsAg(Pfs16-S)的质粒转化含有HBsAg基因基因组拷贝的酵母细胞后,形成了由HBsAg和Pfs16-S组成的病毒样杂交颗粒,其大小与感染乙型肝炎病毒后人血清中存在的颗粒相似。用重组Pfs16痘苗病毒感染的细胞合成了一种约16 kDa的多肽,该多肽与Pfs16特异性多克隆抗体发生反应。用酵母杂交颗粒和/或重组痘苗病毒免疫的动物均产生了Pfs16特异性抗体。这些抗体没有显示出传播阻断活性,但它们有效地减少或消除了子孢子在体外对人肝癌细胞(HepG2-A16)和原代人肝细胞的入侵。

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