Targeting DNA vaccines to myeloid cells using a small peptide.
Targeting DNA vaccines to myeloid cells using a small peptide.
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DOI：
10.1002/eji.201445010
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发表时间：
2015-01
影响因子：
5.4
通讯作者：
Manjunath, N.
中科院分区：
文献类型：
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作者：
Ye, Chunting;Choi, Jang Gi;Abraham, Sojan;Shankar, Premlata;Manjunath, N.
将DNA疫苗靶向树突状细胞（DCs）可大大增强免疫力。尽管已经使用了几种方法将蛋白抗原靶向DC，但目前还没有将DNA疫苗直接靶向DC的方法。在这里，我们表明，来自狂犬病病毒糖蛋白的小肽，融合到鱼精蛋白残基（RVG-P）可以靶向DNA骨髓细胞，包括树突状细胞，导致增强体液和T细胞反应。通过RVG-P编码免疫显性牛痘B8 R基因的DNA疫苗靶向的DC能够在体外再刺激牛痘特异性记忆T细胞。重要的是，单次静脉注射与RVG-P结合的B8 R基因能够引发牛痘特异性T细胞应答，其能够快速清除小鼠中随后的牛痘攻击。此外，在DC中递送DNA足以诱导DC成熟和有效的抗原呈递，而不需要佐剂。最后，通过RVG-P用编码西尼罗河病毒（WNV）prM和E蛋白的DNA疫苗免疫小鼠引起高滴度的WN中和抗体，其保护小鼠免受致死性WNV攻击。因此，RVG-P提供了一种将DNA疫苗靶向骨髓细胞并引发强有力的T细胞和体液免疫应答的试剂。
Targeting DNA vaccines to dendritic cells (DCs) greatly enhances immunity. Although several approaches have been used to target protein antigens to DCs, currently there is no method that targets DNA vaccines directly to DCs. Here, we show that a small peptide derived from the rabies virus glycoprotein, fused to protamine residues (RVG-P) can target DNA to myeloid cells, including DCs, that results in enhanced humoral and T-cell responses. DCs targeted with a DNA vaccine encoding the immunodominant vaccinia B8R gene via RVG-P were able to restimulate vaccinia-specific memory T cells in vitro. Importantly, a single i.v. injection of B8R gene bound to RVG-P was able prime a vaccinia-specific T-cell response that was able to rapidly clear a subsequent vaccinia challenge in mice. Moreover, delivery of DNA in DCs was enough to induce DC maturation and efficient antigen presentation without the need for adjuvants. Finally, immunization of mice with a DNA-vaccine encoding West Nile virus (WNV) prM and E proteins via RVG-P elicited high titers of WN neutralizing antibodies that protected mice from lethal WNV challenge. Thus, RVG-P provides a reagent to target DNA vaccines to myeloid cells and elicit robust T-cell and humoral immune responses.
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影响因子：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
4.4
作者：
Carter, Robert W.;Thompson, Clare;Tough, David F.
通讯作者：
Tough, David F.
影响因子：
3.6
作者：
Demangel, C;Zhou, J;Britton, WJ
通讯作者：
Britton, WJ
DOI：
10.1073/pnas.0711976105
发表时间：
2008-02-19
影响因子：
11.1
作者：
Trumpfheller, Christine;Caskey, Marina;Steinman, Ralph M.
通讯作者：
Steinman, Ralph M.
DOI：
10.1038/mt.2011.190
发表时间：
2011-12
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
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作者：
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