Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
Department of Dermatology, University Medical Center, Johannes Gutenberg-University Mainz, Obere Zahlbacher Straße 63, 55131, Mainz, Germany.
Macromol Biosci. 2017 Oct;17(10). doi: 10.1002/mabi.201700061. Epub 2017 Jul 31.
In this work, the first vaccine is reported based on a PeptoSome, which contains a model antigen (SIINFEKL) and adjuvant (CpG). PeptoSomes are polypept(o)ide-based polymersomes built of a block-copolymer with polysarcosine (PSar) as the hydrophilic block (X = 111) and poly(benzyl-glutamic acid) (PGlu(OBn)) as the hydrophobic one (X = 46). The polypept(o)ide is obtained with low dispersity index of 1.32 by controlled ring-opening polymerization. Vesicle formation by dual centrifugation technique allows for loading of vesicles up to 40 mol%. PeptoSomes are characterized by multiangle dynamic light scattering, static light scattering, and cryogenic transmission electron microscopy (cryoTEM). The PeptoSomes have a hydrodynamic radius of 39.2 nm with a low dispersity (µ = 0.1). The ρ-ratio R /R of 0.95 already indicates that vesicles are formed, which can be confirmed by cryoTEM. Loaded PeptoSomes deliver the antigen (SIINFEKL) and an adjuvant (CpG) simultaneously into dendritic cells (DCs). Upon cellular uptake, dendritic cells are stimulated and activated, which leads to expression of cluster of differentiation CD80, CD86, and MHCII, but induces excretion of proinflammatory cytokines (e.g., TNFα). Furthermore, DC-mediated antigen-specific T-cell proliferation is achieved, thus underlining the enormous potential of PeptoSomes as a versatile platform for vaccination.
在这项工作中，报道了第一个基于 PeptoSome 的疫苗，其中包含模型抗原（SIINFEKL）和佐剂（CpG）。PeptoSomes 是由嵌段共聚物构建的多肽聚合物囊泡，亲水嵌段为多聚丝氨酸（PSar）（X = 111），疏水嵌段为聚（苄基-谷氨酸）（PGlu（OBn））（X = 46）。多肽通过受控开环聚合获得，低分散指数为 1.32。通过双离心技术形成囊泡，允许装载高达 40 mol%的囊泡。PeptoSomes 通过多角度动态光散射、静态光散射和低温透射电子显微镜（cryoTEM）进行表征。PeptoSomes 的水力学半径为 39.2nm，分散度低（µ = 0.1）。ρ-比 R /R 为 0.95 已经表明形成了囊泡，这可以通过 cryoTEM 来证实。负载的 PeptoSomes 同时将抗原（SIINFEKL）和佐剂（CpG）递送至树突状细胞（DC）。在细胞摄取后，树突状细胞被刺激和激活，导致分化簇 CD80、CD86 和 MHCII 的表达，但诱导促炎细胞因子（如 TNFα）的排泄。此外，实现了 DC 介导的抗原特异性 T 细胞增殖，从而强调了 PeptoSomes 作为多功能疫苗平台的巨大潜力。
