Protective Efficacy of Baculovirus Dual Expression System Vaccine Expressing Plasmodium falciparum Circumsporozoite Protein
Protective Efficacy of Baculovirus Dual Expression System Vaccine Expressing Plasmodium falciparum Circumsporozoite Protein
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DOI：
10.1371/journal.pone.0070819
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发表时间：
2013-08-12
期刊：
影响因子：
3.7
通讯作者：
Yoshida, Shigeto
中科院分区：
文献类型：
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作者：
Iyori, Mitsuhiro;Nakaya, Hiroki;Yoshida, Shigeto
我们之前开发了一种基于杆状病毒双表达系统（BDES）的新型疟疾疫苗递送系统。在这个系统中，疟疾抗原的表达是由由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的双启动子驱动的。为了测试该系统作为人类疟疾寄生虫疫苗的潜力，我们研究了新开发的基于bdes的恶性疟原虫环孢子子蛋白疫苗（BDES-PfCSP）在小鼠和恒河猴中的免疫反应。用BDESPfCSP免疫小鼠可诱导具有高PfCSP特异性抗体（Ab）滴度的Th1/ th2混合型免疫应答，并对表达PfCSP的转基因贝氏疟原虫感染的蚊虫叮咬具有显著的保护作用。接下来，我们在恒河猴模型中评估了BDES-PfCSP疫苗的免疫原性。BDES-PfCSP免疫在个别猴子中引起高水平的抗pfcsp抗体反应。此外，免疫猴子的血清显著阻断了孢子子对HepG2细胞的侵袭。结合两种动物模型，我们的研究结果表明，这种新型疫苗平台（BDES）作为疟疾疫苗具有潜在的临床应用价值。
We have previously developed a new malaria vaccine delivery system based on the baculovirus dual expression system (BDES). In this system, expression of malaria antigens is driven by a dual promoter consisting of the baculovirus-derived polyhedrin and mammal-derived cytomegalovirus promoters. To test this system for its potential as a vaccine against human malaria parasites, we investigated immune responses against the newly developed BDES-based Plasmodium falciparum circumsporozoite protein vaccines (BDES-PfCSP) in mice and Rhesus monkeys. Immunization of mice with BDESPfCSP induced Th1/Th2-mixed type immune responses with high PfCSP-specific antibody (Ab) titers, and provided significant protection against challenge from the bites of mosquitoes infected with a transgenic P. berghei line expressing PfCSP. Next, we evaluated the immunogenicity of the BDES-PfCSP vaccine in a rhesus monkey model. Immunization of BDES-PfCSP elicited high levels of anti-PfCSP Ab responses in individual monkeys. Moreover, the sera from the immunized monkeys remarkably blocked sporozoite invasion of HepG2 cells. Taken together with two animal models, our results indicate that this novel vaccine platform (BDES) has potential clinical application as a vaccine against malaria.