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糖基磷脂酰肌醇锚定信号序列增强了编码恶性疟原虫性阶段抗原Pfs230的DNA疫苗的免疫原性。

A glycosylphosphatidylinositol anchor signal sequence enhances the immunogenicity of a DNA vaccine encoding Plasmodium falciparum sexual-stage antigen, Pfs230.

作者信息

Fanning Sarah L, Czesny Beata, Sedegah Martha, Carucci Daniel J, van Gemert Geert Jan, Eling Wijnand, Williamson Kim C

机构信息

Department of Biology, Loyola University Chicago, 6525 North Sheridan Road, Chicago, IL, 60626, USA.

出版信息

Vaccine. 2003 Jul 4;21(23):3228-35. doi: 10.1016/s0264-410x(03)00265-2.

DOI:10.1016/s0264-410x(03)00265-2
PMID:12804852
Abstract

Mammalian expression vectors encoding region C of malaria transmission-blocking vaccine candidate Pfs230 (aa 443-1132) with and without a 3' glycosylphosphatidylinositol (GPI) anchor signal sequence were tested for their immunogenicity in mice. The plasmid containing the GPI anchor signal sequence consistently induced higher titers of anti-Pfs230 antibodies using three delivery systems: intramuscular (i.m.), intradermal (i.d.), and gene gun (g.g.). In contrast, the isotype profile elicited varied depending on the delivery system and was not effected by the presence of the GPI anchor sequence. Both gene gun and intradermal administration induced primarily an IgG1 response, while intramuscular injection induced both IgG1 and IgG2a antibodies. Regardless of the mode of delivery, all the plasmids encoding Pfs230 region C primed for a mixed IgG1/IgG2a response to an intraperitoneal (i.p.) injection of E. coli-produced recombinant Pfs230 region C. None of these vaccination strategies were more effective than r230/MBP.C alone in generating malaria transmission-blocking immunity.

摘要

对编码疟疾传播阻断疫苗候选物Pfs230(氨基酸443 - 1132)C区且带有或不带有3'糖基磷脂酰肌醇(GPI)锚定信号序列的哺乳动物表达载体在小鼠中进行了免疫原性测试。含有GPI锚定信号序列的质粒在三种递送系统(肌肉注射(i.m.)、皮内注射(i.d.)和基因枪(g.g.))下均持续诱导出更高滴度的抗Pfs230抗体。相比之下,所引发的抗体亚型谱因递送系统而异,且不受GPI锚定序列的影响。基因枪和皮内给药主要诱导IgG1应答,而肌肉注射则诱导IgG1和IgG2a抗体。无论递送方式如何,所有编码Pfs230 C区的质粒在腹腔注射(i.p.)大肠杆菌产生的重组Pfs230 C区后均引发了混合的IgG1/IgG2a应答。在产生疟疾传播阻断免疫力方面,这些疫苗接种策略均不比单独的r230/MBP.C更有效。

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