Baculovirus vectors are able to transduce a large variety of mammalian cell types and express transgenes placed under the control of heterologous promoters. In this study, we evaluated the potential of baculovirus vectors for malaria vaccination. To induce efficient CD4(+) and CD8(+) T-cell responses, we produced a series of vectors that display the Plasmodium falciparum circumsporozoite (CS) protein in the virion envelope and/or allow for CS expression upon transduction of mammalian cells. We found that baculovirus vectors can transduce professional antigen-presenting cells and trigger their maturation, which is a prerequisite for efficient antigen presentation. Upon intramuscular injection into mice, the vector that both displayed and expressed CS induced higher anti-CS antibody titers (of the immunoglobulin (IgG)1 and IgG2a type) and a higher frequency of interferon-gamma-producing T cells specific to CS, than the vectors which either only displayed or only expressed CS. The baculovirus CS display/expression vector was also superior in inducing CS-specific CD4(+) and CD8(+) T-cell responses in vitro using human peripheral blood mononuclear cells from naive donors. This, together with the absence of pre-existing immunity to baculoviruses in humans, the absence of viral gene expression in mammalian cells, and the relative low immunogenicity of baculovirus virions, makes these vectors promising tools for vaccination. Furthermore, the ability to produce large amounts in serum-free medium at a low cost adds a further advantage to this vector system.

译文

杆状病毒载体能够转导多种哺乳动物细胞类型并表达在异源启动子控制下的转基因。在这项研究中,我们评估了杆状病毒载体在疟疾疫苗接种中的潜力。为了诱导有效的CD4()和CD8()T细胞应答,我们产生了一系列载体,这些载体在病毒体被膜中显示恶性疟原虫环子孢子(CS)蛋白和/或在哺乳动物细胞转导时允许CS表达。我们发现杆状病毒载体可以转导专业的抗原呈递细胞并触发其成熟,这是有效抗原呈递的前提。在向小鼠肌肉内注射后,既展示又表达CS的载体比CS诱导的抗CS抗体效价更高(免疫球蛋白(IgG)1和IgG2a类型),并且产生的CS特异性干扰素-γT细胞频率更高。仅显示或仅表示CS的向量。杆状病毒CS展示/表达载体在使用来自天真的供体的人外周血单核细胞体外诱导CS特异性CD4()和CD8()T细胞应答方面也表现优异。这加上在人类中不存在针对杆状病毒的预先存在的免疫力,在哺乳动物细胞中不存在病毒基因表达以及杆状病毒毒粒的相对较低的免疫原性,使得这些载体成为用于疫苗接种的有前途的工具。此外,以低成本在无血清培养基中大量生产的能力为该载体系统增加了进一步的优势。

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