A Baculovirus Dual Expression System-Based Malaria Vaccine Induces Strong Protection against Plasmodium berghei Sporozoite Challenge in Mice
A Baculovirus Dual Expression System-Based Malaria Vaccine Induces Strong Protection against Plasmodium berghei Sporozoite Challenge in Mice
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DOI：
10.1128/iai.01226-08
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发表时间：
2009-05-01
影响因子：
3.1
通讯作者：
Matsumoto, Makoto
中科院分区：
文献类型：
--
作者：
Yoshida, Shigeto;Kawasaki, Masanori;Matsumoto, Makoto
我们以前已经表明，一种重组杆状病毒，展示伯氏疟原虫环子孢子蛋白（PbCSP），一个同源的领先的人类疟疾疫苗候选人，对病毒包膜保护60%的小鼠对伯氏疟原虫感染。在这里，我们描述了第二代杆状病毒疫苗的基础上的“杆状病毒双表达系统”，驱动PbCSP表达的双启动子，由串联排列的杆状病毒衍生的多角体蛋白和哺乳动物衍生的巨细胞病毒启动子。基于杆状病毒的PbCSP疫苗不仅在病毒包膜上展示PbCSP，而且在哺乳动物细胞转导后表达PbCSP。在没有外源免疫佐剂的情况下，使用基于杆状病毒的PbCSP疫苗进行免疫接种在小鼠中引发了高PbCSP特异性抗体滴度（主要是免疫球蛋白G1 [IgG 1]和IgG 2a）和PbCSP特异性CD 8（+）T细胞应答，表明存在Th 1和Th 2应答的诱导（混合Th 1/Th 2应答）。重要的是，肌内接种后，基于杆状病毒的PbCSP疫苗赋予针对子孢子攻击的完全保护。因此，基于杆状病毒的PbCSP疫苗诱导针对红细胞前寄生虫的强保护性免疫应答。这些结果为杆状病毒双表达系统引入了一个新的概念，该系统既可作为亚单位疫苗又可作为DNA疫苗，并为目前的人类疫苗递送平台提供了一种有前途的新替代方案。
We have previously shown that a recombinant baculovirus that displays Plasmodium berghei circumsporozoite protein (PbCSP), a homolog of the leading human malaria vaccine candidate, on the viral envelope protected 60% of mice against P. berghei infection. Here, we describe a second-generation baculovirus vaccine based on the "baculovirus dual expression system," which drives PbCSP expression by a dual promoter that consists of tandemly arranged baculovirus-derived polyhedrin and mammal-derived cytomegalovirus promoters. The baculovirus-based PbCSP vaccine not only displayed PbCSP on the viral envelope but also expressed PbCSP upon transduction of mammalian cells. Immunization with the baculovirus-based PbCSP vaccine elicited high PbCSP-specific antibody titers (predominantly immunoglobulin G1 [IgG1] and IgG2a) and PbCSP-specific CD8(+) T-cell responses without extraneous immunological adjuvants in mice, indicating that there was induction of both Th1 and Th2 responses (a mixed Th1/Th2 response). Importantly, upon intramuscular inoculation, the baculovirus-based PbCSP vaccine conferred complete protection against sporozoite challenge. Thus, the baculovirus-based PbCSP vaccine induced strong protective immune responses against preerythrocytic parasites. These results introduce a novel concept for the baculovirus dual expression system that functions as both a subunit vaccine and a DNA vaccine and offer a promising new alternative to current human vaccine delivery platforms.