Intranasal and intramuscular immunization with Baculovirus Dual Expression System-based Pvs25 vaccine substantially blocks Plasmodium vivax transmission
Intranasal and intramuscular immunization with Baculovirus Dual Expression System-based Pvs25 vaccine substantially blocks Plasmodium vivax transmission
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DOI：
10.1016/j.vaccine.2010.06.100
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发表时间：
2010-08-23
期刊：
影响因子：
5.5
通讯作者：
Sinden, Robert E.
中科院分区：
文献类型：
--
作者：
Blagborough, Andrew M.;Yoshida, Shigeto;Sinden, Robert E.
我们最近开发了一种新的基于加州自噬核多角体病毒（AcNPV）的实验性疫苗载体系统，称为“杆状病毒双表达系统”，它通过双启动子驱动疫苗候选抗原的表达，双启动子由串联排列的杆状病毒衍生的多面蛋白和哺乳动物衍生的巨细胞病毒启动子组成。本研究利用该系统制备了一种间日疟原虫传播阻断免疫原（AcNPV-Dual-Pvs25）。AcNPV- dual -Pvs25不仅在AcNPV包膜上显示Pvs25，显示其天然三维结构的各个方面，而且在哺乳动物细胞转导后适当表达免疫原性蛋白。AcNPV-Dual-Pvs25小鼠鼻内和肌内免疫均可诱导高pvs25特异性抗体滴度，特别是IgG1， IgG2a和IgG2b同型，表明混合Thl/Th2反应。重要的是，当使用标准的膜喂养试验用感染间日疟原虫配子体的人血液攻击时，从皮下免疫兔获得的血清显示出显著的传播阻断作用（感染强度降低96%，患病率降低24%）。此外，主动免疫（鼻内和肌肉注射途径）小鼠后，用表达Pvs25的转基因伯氏疟原虫细胞系代替天然Pbs25和Pbs28（克隆Pv525DR3）攻击，显示出强烈的传播阻断反应，卵囊强度降低92.1%（鼻内）和83.8%（肌肉内）。感染率相应下降（分别为88.4%和75.5%）。这项研究为开发针对疟原虫性阶段的疟疾传播阻断疫苗提供了一种新工具，使用杆状病毒双表达系统作为亚基和基于DNA的疫苗。(C) 2010 Elsevier Ltd.版权所有。
We have recently developed a new experimental vaccine vector system based on Autographa californica nucleopolyhedrosis virus (AcNPV) termed the "Baculovirus Dual Expression System", which drives expression of vaccine candidate antigens by a dual promoter that consists of tandemly arranged baculovirus-derived polyhedrin and mammalian-derived CMV promoters. The present study used this system to generate a Plasmodium vivax transmission-blocking immunogen (AcNPV-Dual-Pvs25). AcNPV-Dual-Pvs25 not only displayed Pvs25 on the AcNPV envelope, exhibiting aspects of its native three-dimensional structure, but also expressed appropriately immunogenic protein upon transduction of mammalian cells. Both intranasal and intramuscular immunization of mice with AcNPV-Dual-Pvs25 induced high Pvs25-specific antibody titres, notably of IgG1, IgG2a and IgG2b isotypes, indicating a mixed Thl/Th2 response. Importantly, sera obtained from subcutaneously immunized rabbits exhibited a significant transmission-blocking effect (96% reduction in infection intensity, 24% reduction in prevalence) when challenged with human blood infected with P. vivax gametocytes using the standard membrane feeding assay. Additionally, active immunization (both intranasal and intramuscular routes) of mice followed by challenge using a transgenic P. berghei line expressing Pvs25 in place of native Pbs25 and Pbs28 (clone Pv525DR3) demonstrates a strong transmission-blocking response, with a 92.1% (intranasal) and 83.8% (intramuscular) reduction in oocyst intensity. Corresponding reductions in prevalence of infection were observed (88.4% and 75.5% respectively). This study offers a novel tool for the development of malarial transmission-blocking vaccines against the sexual stages of the parasite, using the Baculovirus Dual Expression System that functions as both a subunit, and DNA based vaccine. (C) 2010 Elsevier Ltd. All rights reserved.