Poly(I:C) is an effective adjuvant for antibody and multi-functional CD4+ T cell responses to Plasmodium falciparum circumsporozoite protein (CSP) and αDEC-CSP in non human primates.
Poly(I:C) is an effective adjuvant for antibody and multi-functional CD4+ T cell responses to Plasmodium falciparum circumsporozoite protein (CSP) and αDEC-CSP in non human primates.
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DOI：
10.1016/j.vaccine.2010.08.098
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发表时间：
2010-10-21
期刊：
影响因子：
5.5
通讯作者：
Seder, Robert A.
中科院分区：
文献类型：
--
作者：
Tewari, Kavita;Flynn, Barbara J.;Boscardin, Silvia B.;Kastenmueller, Kathrin;Salazar, Andres M.;Anderson, Charles A.;Soundarapandian, Velmurugan;Ahumada, Adriana;Keler, Tibor;Hoffman, Stephen L.;Nussenzweig, Michel C.;Steinman, Ralph M.;Seder, Robert A.
开发针对疟疾感染红细胞前阶段的完全有效的疫苗可能需要诱导体液和细胞免疫反应。基于蛋白质的疫苗可以引发如此广泛的免疫力，具体取决于佐剂和蛋白质的配制方式。为了评估这些变量，使用恶性疟原虫 (Pf) 环子孢子蛋白 (CSP) 或克隆到 MG38 中的 CSP 对非人灵长类动物 (NHP) 进行了 3 次免疫，MG38 是一种针对树突状细胞 (DC) 上的内吞受体 DEC-205 (αDEC-CSP) 的单克隆抗体。两种疫苗均使用或不使用聚（I:C）作为佐剂施用。三次免疫后，CSP + Poly(I:C) 组和 αDEC-CSP + Poly(I:C) 组之间分泌细胞因子的 CD4+ T 细胞的数量和质量相当，两种方案均引发多功能细胞因子反应。然而，用 CSP + Poly(I:C) 免疫的 NHP 具有显着更高的 CSP 特异性 IgG 抗体血清滴度和针对 Pf 子孢子的间接免疫荧光抗体 (IFA) 滴度。此外，来自 CSP 或 αDEC-CSP + poly(I:C) 免疫动物的血清在体外限制了子孢子对肝细胞系 (HC04) 的侵袭。为了确定是否可以增强 CSP 特异性反应，所有用 CSP 或 αDEC-CSP + 聚 (I:C) 引发的 NHP 均通过静脉注射单剂量 150,000 个经辐照的 Pf 子孢子 (PfSPZ) 进行加强。值得注意的是，加强免疫对 CSP 特异性免疫没有影响。最后，在实验小鼠模型中，CSP + 聚 ICLC 免疫减少了肝脏中的疟疾寄生虫负担。总而言之，这些数据表明，poly(I:C) 是一种有效的佐剂，可诱导强效抗体，并且基于 CSP 的疫苗可产生 Th1 免疫，为现有基于蛋白质的前红细胞疫苗提供了潜在的替代方案。
Development of a fully effective vaccine against the pre-erythrocytic stage of malaria infection will likely require induction of both humoral and cellular immune responses. Protein based vaccines can elicit such broad-based immunity depending on the adjuvant and how the protein is formulated. Here to assess these variables, non-human primates (NHP) were immunized three times with Plasmodium falciparum (Pf) circumsporozoite protein (CSP) or CSP cloned into MG38, a monoclonal antibody that targets DEC-205 (αDEC-CSP), an endocytic receptor on dendritic cells (DCs). Both vaccines were administered with or without poly(I:C) as adjuvant. Following three immunizations, the magnitude and quality of cytokine secreting CD4+ T cells were comparable between CSP + poly(I:C) and αDEC-CSP + poly(I:C) groups with both regimens eliciting multi-functional cytokine responses. However, NHP immunized with CSP + poly(I:C) had significantly higher serum titers of CSP-specific IgG antibodies and indirect immunofluorescent antibody (IFA) titers against Pf sporozoites. Furthermore, sera from both CSP or αDEC-CSP + poly(I:C) immunized animals limited sporozoite invasion of a hepatocyte cell line (HC04) in vitro. To determine whether CSP-specific responses could be enhanced, all NHP primed with CSP or αDEC-CSP + poly(I:C) were boosted with a single dose of 150,000 irradiated Pf sporozoites (PfSPZ) intravenously. Remarkably, boosting had no effect on the CSP-specific immunity. Finally, immunization with CSP + poly-ICLC reduced malaria parasite burden in the liver in an experimental mouse model. Taken together, these data showing that poly(I:C) is an effective adjuvant for inducing potent antibody and Th1 immunity with CSP based vaccines offers a potential alternative to the existing protein based pre-erythrocytic vaccines.
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影响因子：
64.8
作者：
Mueller, AK;Labaied, M;Matuschewski, K
通讯作者：
Matuschewski, K
影响因子：
64.5
作者：
CERAMI, C;FREVERT, U;NUSSENZWEIG, V
通讯作者：
NUSSENZWEIG, V
影响因子：
3.1
作者：
CLYDE, DF;MCCARTHY, VC;HORNICK, RB
通讯作者：
HORNICK, RB
影响因子：
4.4
作者：
Granelli-Piperno, A;Pritsker, A;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
82.9
作者：
Darrah, Patricia A.;Patel, Dipti T.;Seder, Robert A.
通讯作者：
Seder, Robert A.