TLR9-targeted biodegradable nanoparticles as immunization vectors protect against West Nile encephalitis.
TLR9-targeted biodegradable nanoparticles as immunization vectors protect against West Nile encephalitis.
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DOI：
10.4049/jimmunol.1000768
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发表时间：
2010-09-01
期刊：
影响因子：
--
通讯作者：
Fahmy TM
中科院分区：
文献类型：
--
作者：
Demento SL;Bonafé N;Cui W;Kaech SM;Caplan MJ;Fikrig E;Ledizet M;Fahmy TM
许多感染因子，包括黄病毒、登革热病毒和西尼罗河病毒，迫切需要激活体液和细胞介导的免疫反应的疫苗。一种新的方法将极大地促进疫苗的开发，在这种方法中，纳米级模块（抗原、佐剂和载体）被组装成优化的单元，以刺激对特定病原体的免疫反应。为了实现这一目标，我们配制了可生物降解的纳米颗粒，装载Ag，表面修饰病原体相关分子模式CpG寡脱氧核苷酸。我们选择使用来自WN病毒的重组包膜蛋白Ag来评估我们的构建，并测试了该系统在引发体液和细胞反应以及提供对活病毒的保护方面的效率。用该系统免疫的动物表现出强烈的Th1免疫反应极化，而用佐剂氢氧化铝免疫的动物则主要偏向th2免疫反应。与未经修饰的纳米颗粒或氢氧化铝相比，用CpG寡脱氧核苷酸修饰的纳米颗粒免疫可产生更多的循环效应T细胞和更高的ag特异性淋巴细胞活性。最终，与明矾相比，该系统在WN病毒脑炎小鼠模型中提供了更好的保护。
Vaccines that activate humoral and cell-mediated immune responses are urgently needed for many infectious agents, including the flaviviruses dengue and West Nile (WN) virus. Vaccine development would be greatly facilitated by a new approach, in which nanoscale modules (Ag, adjuvant, and carrier) are assembled into units that are optimized for stimulating immune responses to a specific pathogen. Toward that goal, we formulated biodegradable nanoparticles loaded with Ag and surface modified with the pathogen-associated molecular pattern CpG oligodeoxynucleotides. We chose to evaluate our construct using a recombinant envelope protein Ag from the WN virus and tested the efficiency of this system in eliciting humoral and cellular responses and providing protection against the live virus. Animals immunized with this system showed robust humoral responses polarized toward Th1 immune responses compared with predominately Th2-biased responses with the adjuvant aluminum hydroxide. Immunization with CpG oligodeoxynucleotide-modified nanoparticles resulted in a greater number of circulating effector T cells and greater activity of Ag-specific lymphocytes than unmodified nanoparticles or aluminum hydroxide. Ultimately, compared with alum, this system offered superior protection in a mouse model of WN virus encephalitis.
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