Here, a vaccine delivery system is developed that attains sustained release of antigens (ovalbumin; model antigen) and adjuvants (CpG-DNA; oligodeoxynucleotides containing unmethylated cytosine-guanine motifs) using biodegradable temperature-responsive injectable polymers (IP). Previously a biodegradable IP system was prepared that exhibited a temperature-responsive sol-to-gel transition and subsequent chemical cross-linking. The IP system used triblock copolymers, poly(ε-caprolactone-co-glycolide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-glycolide) (tri-PCG) and a polymer whose termini were converted to N-hydroxysuccinimide esters (tri-PCG-OSu). OVA and CpG-DNA sustained release was achieved using tri-PCG-based IP systems in vitro. Moreover, the release of CpG-DNA was delayed using an IP system containing tri-PCG-OSu mixed with poly(L-lysine) (PLL). Subcutaneous administration of the tri-PCG-based IP gel vaccine induced stronger humoral and cellular immune responses in mice than in those without IP administration. The Tri-PCG-OSu IP gel maintained high OVA-specific IgG titers for 22 weeks. In contrast, the tri-PCG IP gel exhibits a relatively rapid release of CpG DNA in vitro, predominantly inducing cellular immune responses. Furthermore, the tri-PCG IP gel shows a potent antitumor effect against OVA-expressing T lymphoma (E.G7-OVA) and extends the survival duration of mice. Therefore, tri-PCG-based IP systems are promising vaccine platforms for controlling the release of antigens and adjuvants to enhance the humoral and cellular immune responses.

中文翻译：

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使用温度响应型可生物降解注射聚合物持续释放抗原和 CpG-DNA：诱导免疫反应的性能

在这里，开发了一种疫苗递送系统，使用可生物降解的温度响应性可注射聚合物（IP）实现抗原（卵清蛋白；模型抗原）和佐剂（CpG-DNA；含有未甲基化胞嘧啶-鸟嘌呤基序的寡脱氧核苷酸）的持续释放。之前制备的可生物降解 IP 系统表现出温度响应性溶胶到凝胶的转变以及随后的化学交联。 IP系统使用三嵌段共聚物，聚(ε-己内酯-共-乙交酯) -b-聚(乙二醇)-b-聚(ε-己内酯-共-乙交酯)(tri-PCG)和末端转化的聚合物N-羟基琥珀酰亚胺酯（三-PCG-OSu）。使用基于 tri-PCG 的 IP 系统在体外实现了 OVA 和 CpG-DNA 的持续释放。此外，使用含有与聚（L-赖氨酸）混合的三-PCG-OSu（PLL）的IP系统延迟了CpG-DNA的释放。与未进行IP注射的小鼠相比，皮下注射基于三PCG的IP凝胶疫苗在小鼠中诱导了更强的体液和细胞免疫反应。 Tri-PCG-OSu IP 凝胶可在 22 周内保持高 OVA 特异性 IgG 滴度。相比之下，tri-PCG IP 凝胶在体外表现出相对快速的 CpG DNA 释放，主要诱导细胞免疫反应。此外，tri-PCG IP 凝胶对表达 OVA 的 T 淋巴瘤 (E.G7-OVA) 显示出有效的抗肿瘤作用，并延长了小鼠的生存时间。因此，基于三PCG的IP系统是有前途的疫苗平台，用于控制抗原和佐剂的释放，以增强体液和细胞免疫反应。