The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine
The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine
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DOI：
10.1073/pnas.0711976105
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发表时间：
2008-02-19
影响因子：
11.1
通讯作者：
Steinman, Ralph M.
中科院分区：
文献类型：
--
作者：
Trumpfheller, Christine;Caskey, Marina;Steinman, Ralph M.
CD4(+) Th1型免疫与抵抗全球性传染病有关。为了提高人类免疫缺陷病毒（HIV）疫苗诱导的T细胞免疫的功效，我们正在开发一种基于蛋白质的方法，直接利用完整淋巴组织中树突状细胞（dc）的功能。疫苗蛋白通过抗体（一种抗原呈递受体）选择性地递送到dc。我们发现，多核糖素：多核糖素酸（poly IC）独立地作为佐剂，允许dc靶向蛋白在气道粘膜表面诱导保护性CD4+ T细胞反应。在两剂dec靶向的HIV gag p24和poly IC后，应答性CD4(+) T细胞具有与保护功能相关的定性特征。T细胞同时产生ifn - γ、肿瘤坏死因子(TNF)- α和IL-2，并且长时间大量产生。T细胞也会增殖并继续分泌ifn - γ以响应HIV gag p24。poly IC的辅助作用需要toll样受体（TLR） 3和黑色素瘤分化相关基因-5 （MDA5）受体，但其类似物poly IC12U只需要TLR3。我们建议将聚IC作为dc靶向疫苗的佐剂进行试验，以诱导大量具有增殖能力的多功能CD4(+) Th1细胞。
CD4(+) Th1 type immunity is implicated in resistance to global infectious diseases. To improve the efficacy of T cell immunity induced by human immunodeficiency virus (HIV) vaccines, we are developing a protein-based approach that directly harnesses the function of dendritic cells (DCs) in intact lymphoid tissues. Vaccine proteins are selectively delivered to DCs by antibodies to IDEC-205/CD205, a receptor for antigen presentation. We find that polyriboinosinic:polyribocytidylic acid (poly IC) independently serves as an adjuvant to allow a DC-targeted protein to induce protective CD4+ T cell responses at a mucosal surface, the airway. After two doses of DEC-targeted, HIV gag p24 along with poly IC, responder CD4(+) T cells have qualitative features that have been correlated with protective function. The T cells simultaneously make IFN-gamma, tumor necrosis factor (TNF)-alpha, and IL-2, and in high amounts for prolonged periods. The T cells also proliferate and continue to secrete IFN-gamma in response to HIV gag p24. The adjuvant role of poly IC requires Toll-like receptor (TLR) 3 and melanoma differentiation-associated gene-5 (MDA5) receptors, but its analog Poly IC12U requires only TLR3. We suggest that poly IC be tested as an adjuvant with DC-targeted vaccines to induce numerous multifunctional CD4(+) Th1 cells with proliferative capacity.