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Active targeting of early and mid-stage atherosclerotic plaques using self-assembled peptide amphiphile micelles.利用自组装肽两亲胶束主动靶向早期和中期动脉粥样硬化斑块。
Biomaterials. 2014 Oct;35(30):8678-86. doi: 10.1016/j.biomaterials.2014.06.054. Epub 2014 Jul 16.
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Development of multinuclear polymeric nanoparticles as robust protein nanocarriers.多核聚合物纳米颗粒作为坚固蛋白质纳米载体的开发。
Angew Chem Int Ed Engl. 2014 Aug 18;53(34):8975-9. doi: 10.1002/anie.201404766. Epub 2014 Jul 2.
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Recent progress in adjuvant discovery for peptide-based subunit vaccines.基于肽的亚单位疫苗佐剂发现的最新进展。
Hum Vaccin Immunother. 2014;10(3):778-96. doi: 10.4161/hv.27332. Epub 2013 Dec 3.
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Nanoparticle vaccines.纳米颗粒疫苗。
Vaccine. 2014 Jan 9;32(3):327-37. doi: 10.1016/j.vaccine.2013.11.069. Epub 2013 Dec 2.
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The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell responses to peptide antigens without inflammation.利用自佐剂纳米纤维疫苗引发针对肽抗原的高亲和力 B 细胞反应而不引起炎症。
Biomaterials. 2013 Nov;34(34):8776-85. doi: 10.1016/j.biomaterials.2013.07.063. Epub 2013 Aug 13.
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Peptide contour length determines equilibrium secondary structure in protein-analogous micelles.肽链轮廓长度决定了类似蛋白质的胶束中的平衡二级结构。
Biopolymers. 2013 Sep;99(9):573-81. doi: 10.1002/bip.22217.
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Conformational B-cell epitope prediction on antigen protein structures: a review of current algorithms and comparison with common binding site prediction methods.抗原蛋白结构上的构象 B 细胞表位预测:当前算法综述及与常见结合位点预测方法比较。
PLoS One. 2013 Apr 19;8(4):e62249. doi: 10.1371/journal.pone.0062249. Print 2013.
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Persistent antigen at vaccination sites induces tumor-specific CD8⁺ T cell sequestration, dysfunction and deletion.疫苗接种部位持续存在的抗原诱导肿瘤特异性 CD8+T 细胞隔离、功能障碍和缺失。
Nat Med. 2013 Apr;19(4):465-72. doi: 10.1038/nm.3105. Epub 2013 Mar 3.
9
Long-term antibody memory induced by synthetic peptide vaccination is protective against Streptococcus pyogenes infection and is independent of memory T cell help.合成肽疫苗接种诱导的长期抗体记忆可预防化脓性链球菌感染,且独立于记忆 T 细胞辅助。
J Immunol. 2013 Mar 15;190(6):2692-701. doi: 10.4049/jimmunol.1202333. Epub 2013 Feb 11.
10
M-protein-derived conformational peptide epitope vaccine candidate against Group A Streptococcus.针对 A 组链球菌的 M 蛋白衍生构象肽表位疫苗候选物。
Curr Drug Deliv. 2013 Feb;10(1):39-45. doi: 10.2174/1567201811310010007.

肽两亲性胶束自我佐剂化A群链球菌疫苗接种。

Peptide amphiphile micelles self-adjuvant group A streptococcal vaccination.

作者信息

Trent Amanda, Ulery Bret D, Black Matthew J, Barrett John C, Liang Simon, Kostenko Yulia, David Natalie A, Tirrell Matthew V

机构信息

Biomolecular Science and Engineering Program, University of California, Santa Barbara, California, 93106, USA.

出版信息

AAPS J. 2015 Mar;17(2):380-8. doi: 10.1208/s12248-014-9707-3. Epub 2014 Dec 20.

DOI:10.1208/s12248-014-9707-3
PMID:25527256
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4365084/
Abstract

Delivery system design and adjuvant development are crucially important areas of research for improving vaccines. Peptide amphiphile micelles are a class of biomaterials that have the unique potential to function as both vaccine delivery vehicles and self-adjuvants. In this study, peptide amphiphiles comprised of a group A streptococcus B cell antigen (J8) and a dialkyl hydrophobic moiety (diC16) were synthesized and organized into self-assembled micelles, driven by hydrophobic interactions among the alkyl tails. J8-diC16 formed cylindrical micelles with highly α-helical peptide presented on their surfaces. Both the micelle length and secondary structure were shown to be enhanced by annealing. When injected into mice, J8-diC16 micelles induced a strong IgG1 antibody response that was comparable to soluble J8 peptide supplemented with two classical adjuvants. It was discovered that micelle adjuvanticity requires the antigen be a part of the micelle since separation of J8 and the micelle was insufficient to induce an immune response. Additionally, the diC16 tail appears to be non-immunogenic since it does not stimulate a pathogen recognition receptor whose agonist (Pam3Cys) possesses a very similar chemical structure. The research presented in this paper demonstrates the promise peptide amphiphile micelles have in improving the field of vaccine engineering.

摘要

递送系统设计和佐剂开发是改进疫苗的至关重要的研究领域。肽两亲性胶束是一类生物材料,具有作为疫苗递送载体和自佐剂的独特潜力。在本研究中,合成了由A组链球菌B细胞抗原(J8)和二烷基疏水部分(二C16)组成的肽两亲物,并通过烷基尾部之间的疏水相互作用将其组装成自组装胶束。J8-二C16形成了表面呈现高度α-螺旋肽的圆柱形胶束。通过退火显示胶束长度和二级结构均得到增强。当注射到小鼠体内时,J8-二C16胶束诱导出强烈的IgG1抗体反应,这与补充了两种经典佐剂的可溶性J8肽相当。研究发现,胶束佐剂活性要求抗原成为胶束的一部分,因为J8与胶束分离不足以诱导免疫反应。此外,二C16尾部似乎无免疫原性,因为它不会刺激其激动剂(Pam3Cys)具有非常相似化学结构的病原体识别受体。本文提出的研究证明了肽两亲性胶束在改善疫苗工程领域方面的前景。