An Albumin-binding Polypeptide Both Targets Cytotoxic T Lymphocyte Vaccines to Lymph Nodes and Boosts Vaccine Presentation by Dendritic Cells.
An Albumin-binding Polypeptide Both Targets Cytotoxic T Lymphocyte Vaccines to Lymph Nodes and Boosts Vaccine Presentation by Dendritic Cells.
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作者：
Wang P;Zhao P;Dong S;Xu T;He X;Chen M
原理：白蛋白结合载体已被证明将细胞毒性T淋巴细胞(CTL)疫苗靶向淋巴结(LNS)，并提高疫苗的效力。然而，目前还不清楚疗效的改善是否仅仅是由于LN靶向，这促使了这项研究。方法：首先，我们构建了一个由白蛋白结合域(ABD)和免疫耐受弹性蛋白样多肽(ITEP)组成的融合蛋白。然后，我们检测了这种称为Abd-ITEP的融合蛋白与小鼠血清白蛋白(MSA)的结合。接下来，我们评估了Abd-ITEP在LNS和LNS中的树突状细胞(DC)中的积聚。我们还分析了Abd-ITEP提供的疫苗的抗原呈递和体外T细胞激活，并研究了呈递和激活结果的可能机制。最后，我们检测了Abd-ITEP疫苗在体内诱导的CTL反应。结果：ABD-ITEP与MSA结合较强，亲和力为1.41 nM。这种白蛋白结合载体Abd-ITEP在LNS中的蓄积量是未与白蛋白结合的对照载体ITEP的3倍以上。ABD-ITEP在LNS树突状细胞中的蓄积也是ITEP的4倍。最重要的是，Abd-ITEP显著增强了其疫苗有效载荷的抗原呈递和由其有效载荷诱导的T细胞激活。这种增强作用依赖于MSA与Abd-ITEP之间形成的络合物。同时，MSA/Abd-ITEP复合体在酸性亚细胞室中的稳定性增强，在DC中的胞浆蓄积增加，这可能是该复合体增强疫苗呈递能力的原因。最后，当Abd-ITEP被用来运送来自自身和非自身抗原的CTL疫苗时，它在任何一种情况下都将疫苗诱导的反应提高了2倍。结论：ABD-ITEP不仅针对LNS的疫苗，而且促进DC对疫苗的呈递。白蛋白结合载体有多种机制来提高CTL疫苗的效力。
Rationale: Albumin-binding carriers have been shown to target cytotoxic T lymphocyte (CTL) vaccines to lymph nodes (LNs) and improve the efficacy of the vaccines. However, it was not clear whether the improved efficacy is solely due to the LN targeting, which prompted this study. Methods: First, we generated a fusion protein consisting of an albumin-binding domain (ABD) and an immune-tolerant elastin-like polypeptide (iTEP). Then, we examined the binding between this fusion protein, termed ABD-iTEP, and mouse serum albumin (MSA). Next, we evaluated the accumulation of ABD-iTEP in LNs and dendritic cells (DCs) in the LNs. We also analyzed antigen presentation and in vitro T cell activation of vaccines that were delivered by ABD-iTEP and investigated possible underlying mechanisms of the presentation and activation results. Last, we measured CTL responses induced by ABD-iTEP-delivered vaccines in vivo. Results: ABD-iTEP bound with MSA strongly with an affinity of 1.41 nM. This albumin-binding carrier, ABD-iTEP, accumulated in LNs 3-fold more than iTEP, a control carrier that did not bind with albumin. ABD-iTEP also resulted in 4-fold more accumulation in DCs in the LNs than iTEP. Most importantly, ABD-iTEP drastically enhanced the antigen presentation of its vaccine payloads and the T cell activation induced by its payloads. The enhancement was dependent on the formation of the complex between MSA and ABD-iTEP. Meanwhile, the MSA/ABD-iTEP complex was found to have increased stability in acidic subcellular compartments and increased cytosolic accumulation in DCs, which might explain the enhanced vaccine presentation resulting from the complex. Finally, when ABD-iTEP was used to deliver CTL vaccines derived from both self- and non-self-antigens, it boosted the vaccine-induced responses by 2-fold in either case. Conclusion: ABD-iTEP not only targets vaccines to LNs but also promotes the presentation of the vaccines by DCs. Albumin-binding carriers have more than one mechanism to boost the efficacy of CTL vaccines.
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DOI：
10.1128/cdli.8.3.628-631.2001
发表时间：
2001-05-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Ghanekar, SA;Nomura, LE;Maino, VC
通讯作者：
Maino, VC
影响因子：
2.2
作者：
Harrell, Maria I.;Iritani, Brian M.;Ruddell, Alanna
通讯作者：
Ruddell, Alanna
影响因子：
4.8
作者：
Andersen, Jan Terje;Pehrson, Rikard;Ekblad, Caroline
通讯作者：
Ekblad, Caroline
影响因子：
4.4
作者：
Bourquin, Carole;Anz, David;Endres, Stefan
通讯作者：
Endres, Stefan
影响因子：
15.9
作者：
Hanson, Melissa C.;Crespo, Monica R.;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.