Immune-tolerant elastin-like polypeptides (iTEPs) and their application as CTL vaccine carriers.
Immune-tolerant elastin-like polypeptides (iTEPs) and their application as CTL vaccine carriers.
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DOI：
10.3109/1061186x.2015.1077847
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发表时间：
2016
影响因子：
4.5
通讯作者：
Chen M
中科院分区：
文献类型：
--
作者：
Cho S;Dong S;Parent KN;Chen M
细胞毒性T淋巴细胞（CTL）疫苗载体是已知的，以提高疫苗的效力，但寻找更有效的载体是必要的。弹性蛋白样多肽（ELP）已被研究用于许多医学应用，但不是作为CTL疫苗载体。我们的目标是使用一种新的多肽工程实践来创建免疫耐受的ELP，并使用ELP来创建CTL疫苗载体。根据多肽的体液免疫原性和ELP的相变特性，制备了4组新型ELP，称为免疫耐受性弹性蛋白样多肽（iTEP）。iTEP在小鼠中是非免疫原性的。通过浊度测定证实了它们的相变特征。由两亲性iTEP共聚物加上CTL肽疫苗SIINFEKL组装iTEP纳米颗粒（NP）。NP促进了树突状细胞对疫苗的呈递，并增强了疫苗诱导的CTL应答。建立了一个新的ELP设计和开发实践。iTEPs的非典型基序和免疫耐受性质拓宽了我们对ELP的见解。ELP首次成功地用作CTL疫苗的载体。同时工程化免疫耐受和功能肽材料是可行的。ELP是一种很有前途的CTL疫苗载体。
Cytotoxic T lymphocyte (CTL) vaccine carriers are known to enhance the efficacy of vaccines, but a search for more effective carriers is warranted. Elastin-like polypeptides (ELPs) have been examined for many medical applications but not as CTL vaccine carriers. We aimed to create immune tolerant ELPs using a new polypeptide engineering practice and create CTL vaccine carriers using the ELPs. Four sets of novel ELPs, termed immune-tolerant elastin-like polypeptide (iTEP) were generated according to the principles dictating humoral immunogenicity of polypeptides and phase transition property of ELPs. The iTEPs were non-immunogenic in mice. Their phase transition feature was confirmed through a turbidity assay. An iTEP nanoparticle (NP) was assembled from an amphiphilic iTEP copolymer plus a CTL peptide vaccine, SIINFEKL. The NP facilitated the presentation of the vaccine by dendritic cells and enhanced vaccine-induced CTL responses. A new ELP design and development practice was established. The non-canonical motif and the immune tolerant nature of the iTEPs broaden our insights about ELPs. ELPs, for the first time, were successfully used as carriers for CTL vaccines. It is feasible to concurrently engineer both immune-tolerant and functional peptide materials. ELPs are a promising type of CTL vaccine carriers.