Division of Immunology, Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
Division of Immunology, Department of Biology, University of Konstanz, 78457 Konstanz, Germany; Biotechnology Institute Thurgau (BITg) at the University of Konstanz, 8280 Kreuzlingen, Switzerland.
Eur J Pharm Sci. 2022 Aug 1;175:106209. doi: 10.1016/j.ejps.2022.106209. Epub 2022 May 15.
The essential role of tissue-resident memory T cells (T cells) in offering protection from recurring infections and malignant tumors is becoming increasingly clear. Due to their presence in many barrier tissues, T cells are ideally located to rapidly respond to re-encountered pathogens. Moreover, a host of studies has shown that the quantity of T cells correlates with increased survival rates in cancer patients. Therefore, vaccination strategies which induce a strong and sustained T cell response are particularly promising. In this study we show that this response can be induced by employing a prime-boost vaccination strategy using biodegradable poly (D,L-lactide-co-glycolide) microspheres (PLGA MS). A subcutaneous prime immunization followed by an intranasal boost immunization led to a strong T cell response in the lungs of mice 6 days after the boost vaccination. Although numbers subsequently declined, T cells were still detectable 60 days after vaccination. Functionally, we observed that immunized mice were protected from lung metastasis formation and tumor growth in a B16Bl6 melanoma model. Furthermore, the T cells induced by PLGA MS immunization provided protection in an infectious model using a recombinant influenza A virus (IAV). Taken together, these results show that the ability of PLGA MS to induce a strong T cell response further supports their use as a potent vaccine.
组织驻留记忆 T 细胞（T 细胞）在提供免受反复感染和恶性肿瘤保护方面的重要作用变得越来越明显。由于它们存在于许多屏障组织中，T 细胞非常适合快速应对再次遇到的病原体。此外，大量研究表明，T 细胞的数量与癌症患者生存率的提高相关。因此，诱导强烈和持续的 T 细胞反应的疫苗接种策略特别有前途。在这项研究中，我们表明，这种反应可以通过使用可生物降解的聚（D，L-丙交酯-co-乙交酯）微球（PLGA MS）进行初免-加强疫苗接种策略来诱导。在加强免疫接种后 6 天，皮下初免免疫接种后进行鼻内加强免疫接种导致小鼠肺部出现强烈的 T 细胞反应。尽管随后数量下降，但在接种疫苗 60 天后仍可检测到 T 细胞。功能上，我们观察到免疫小鼠在 B16Bl6 黑色素瘤模型中免受肺转移形成和肿瘤生长的保护。此外，PLGA MS 免疫诱导的 T 细胞在使用重组流感 A 病毒（IAV）的感染模型中提供了保护。总之，这些结果表明，PLGA MS 诱导强烈 T 细胞反应的能力进一步支持其作为有效疫苗的使用。
