Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara
Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara
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DOI：
10.1073/pnas.0406381102
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发表时间：
2005-03-29
影响因子：
11.1
通讯作者：
Hill, AVS
中科院分区：
文献类型：
--
作者：
Webster, DP;Dunachie, S;Hill, AVS
疟疾是一个重大的全球健康问题，迫切需要有效的疫苗。涉及质粒DNA和重组修饰的牛痘病毒安卡拉编码的肝脏阶段疟疾抗原的初免-加强疫苗接种方案已显示对T细胞具有强大的免疫原性，并且能够诱导针对人类实验性疟疾攻击的部分保护，表现为寄生虫血症专利时间的延迟。在这里，我们报告，取代质粒DNA作为引发载体与特定的减毒重组鸡痘病毒，FP 9，疫苗在这样的引发-加强制度可以引起完全无菌保护，可以持续20个月。20个月时的保护与持续记忆有关，但与效应T细胞反应无关。各种免疫方案的保护功效与诱导的免疫反应的强度相关，支持最大化持久T细胞免疫原性的策略，以开发更有效的针对恶性疟原虫疟疾的肝脏期疫苗。
Malaria is a major global health problem for which an effective vaccine is required urgently. Prime-boost vaccination regimes involving plasmid DNA and recombinant modified vaccinia virus Ankara-encoding liver-stage malaria antigens have been shown to be powerfully immunogenic for T cells and capable of inducing partial protection against experimental malaria challenge in humans, manifested as a delay in time to patent parasitemia. Here, we report that substitution of plasmid DNA as the priming vector with a specific attenuated recombinant fowlpox virus, FP9, vaccine in such prime-boost regimes can elicit complete sterile protection that can last for 20 months. Protection at 20 months was associated with persisting memory but not effector T cell responses. The protective efficacy of various immunization regimes correlated with the magnitude of induced immune responses, supporting the strategy of maximizing durable T cell immunogenicity to develop more effective liver-stage vaccines against Plasmodium falciparum malaria.