Novel plant virus-based vaccine induces protective cytotoxic T-lymphocyte-mediated antiviral immunity through dendritic cell maturation
Novel plant virus-based vaccine induces protective cytotoxic T-lymphocyte-mediated antiviral immunity through dendritic cell maturation
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DOI：
10.1128/jvi.01811-07
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发表时间：
2008-01-01
影响因子：
5.4
通讯作者：
Lamarre, Alain
中科院分区：
文献类型：
--
作者：
Lacasse, Patrick;Denis, Jerome;Lamarre, Alain
目前使用的疫苗主要通过产生中和抗体来保护。然而，抗体对大多数需要细胞毒性T淋巴细胞（CTL）积极参与的慢性病毒感染几乎没有保护作用。病毒样颗粒（VLP）已被证明是细胞介导的免疫应答的有效诱导剂，但通常需要给予佐剂。我们最近报道了一种新的VLP系统的产生，利用自组装特性的番木瓜花叶病毒（PapMV）外壳蛋白。我们在这里表明，鼠脾树突状细胞（DC）在体内摄取PapMV样颗粒导致其成熟，这表明它们具有内在的澄清剂样特性。用展示淋巴细胞性脉络丛脑膜炎病毒（LCMV）p33免疫显性CTL表位（PapMV-p33）的PapMV样颗粒脉冲的DC有效地加工病毒表位并将其交叉呈递给p33特异性转基因T细胞。重要的是，CTL表位也在体内被适当地加工和呈递，因为用PapMV-p33免疫p33特异性T细胞受体转基因小鼠诱导大量特异性CTL的活化。在不存在佐剂的情况下用PapMV-p33 VLP免疫的C57 BL/6小鼠产生p33特异性效应CTL，其在LCMV攻击后迅速扩增，并以剂量依赖性方式保护接种疫苗的小鼠免受LCMV感染。这些结果证明了这种新的基于植物病毒的疫苗接种平台在诱导DC成熟导致保护性CTL应答中的效率。
Currently used vaccines protect mainly through the production of neutralizing antibodies. However, antibodies confer little or no protection for a majority of chronic viral infections that require active involvement of cytotoxic T lymphocytes (CTLs). Virus-like particles (VLPs) have been shown to be efficient inducers of cell-mediated immune responses, but administration of an adjuvant is generally required. We recently reported the generation of a novel VLP system exploiting the self-assembly property of the papaya mosaic virus (PapMV) coat protein. We show here that uptake of PapMV-like particles by murine splenic dendritic cells (DCs) in vivo leads to their maturation, suggesting that they possess intrinsic adjuvant-like properties. DCs pulsed with PapMV-like particles displaying the lymphocytic choriomeningitis virus (LCMV) p33 immunodominant CTL epitope (PapMV-p33) efficiently process and cross-present the viral epitope to p33-specific transgenic T cells. Importantly, the CTL epitope is also properly processed and presented in vivo, since immunization of p33-specific T-cell receptor transgenic mice with PapMV-p33 induces the activation of large numbers of specific CTLs. C57BL/6 mice immunized with PapMV-p33 VLPs in the absence of adjuvant develop p33-specific effector CTLs that rapidly expand following LCMV challenge and protect vaccinated mice against LCMV infection in a dose-dependent manner. These results demonstrate the efficiency of this novel plant virus-based vaccination platform in inducing DC maturation leading to protective CTL responses.