Yellow fever 17D as a vaccine vector for microbial CTL epitopes: protection in a rodent malaria model.
Yellow fever 17D as a vaccine vector for microbial CTL epitopes: protection in a rodent malaria model.
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DOI：
10.1084/jem.20041526
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发表时间：
2005-01-17
影响因子：
15.3
通讯作者：
Nussenzweig, RS
中科院分区：
文献类型：
--
作者：
Tao, D;Barba-Spaeth, G;Rai, U;Nussenzweig, V;Rice, CM;Nussenzweig, RS
黄热病疫苗17D(17D)是安全的，在单剂免疫后，可产生持久的、可能是终身的保护性免疫。在不发达国家提供人类疫苗面临的主要挑战之一是需要多次注射才能达到完全效果。为了验证17D作为微生物T细胞表位的载体，我们将约氏疟原虫环子孢子蛋白(CS)的H-2Kd限制性CTL表位插入到17D非结构蛋白NS2B和NS3之间。重组病毒17D-Py在体内和体外均具有复制能力和稳定性。单次皮下注射105pfu可将肝脏中的寄生虫负担减少70%∼。高水平的保护在免疫后4至8周持续，但即使在24周后仍有显著效果。因此，插入17D的外来T细胞表位的免疫原性模仿了人类疫苗的一些显著特性。用17D-Py免疫，然后用辐照的子孢子加强免疫，可使90%的小鼠产生不育免疫。这一发现表明，住在流行地区的接种疫苗的个人的免疫反应可能会因受感染的蚊子的叮咬而持续和放大。
The yellow fever vaccine 17D (17D) is safe, and after a single immunizing dose, elicits long-lasting, perhaps lifelong protective immunity. One of the major challenges facing delivery of human vaccines in underdeveloped countries is the need for multiple injections to achieve full efficacy. To examine 17D as a vector for microbial T cell epitopes, we inserted the H-2Kd–restricted CTL epitope of the circumsporozoite protein (CS) of Plasmodium yoelii between 17D nonstructural proteins NS2B and NS3. The recombinant virus, 17D-Py, was replication competent and stable in vitro and in vivo. A single subcutaneous injection of 105 PFU diminished the parasite burden in the liver by ∼70%. The high level of protection lasted between 4 and 8 wk after immunization, but a significant effect was documented even 24 wk afterwards. Thus, the immunogenicity of a foreign T cell epitope inserted into 17D mimics some of the remarkable properties of the human vaccine. Priming with 17D-Py followed by boosting with irradiated sporozoites conferred sterile immunity to 90% of the mice. This finding indicates that the immune response of vaccine-primed individuals living in endemic areas could be sustained and magnified by the bite of infected mosquitoes.
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影响因子：
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