Department of Biomedical Molecular Biology, Ghent University, Zwijnaarde, Belgium.
J Immunol. 2010 Jan 1;184(1):203-11. doi: 10.4049/jimmunol.0803591. Epub 2009 Nov 30.
Because of their large surface area, the lungs appear an attractive route for noninvasive vaccine delivery, harboring the potential to induce local mucosal immune responses in addition to systemic immunity. To evoke adaptive immunity, Ags require the addition of adjuvants that not only enhance the strength of the immune response but also determine the type of response elicited. In this study, we evaluate the adjuvant characteristics of polyelectrolyte microcapsules (PEMs) consisting of the biopolymers dextran-sulfate and poly-L-arginine. PEMs form an entirely new class of microcapsules that are generated by the sequential adsorption of oppositely charged polymers (polyelectrolytes) onto a sacrificial colloidal template, which is subsequently dissolved leaving a hollow microcapsule surrounded by a thin shell. Following intratracheal instillation, PEMs were not only efficiently taken up by APCs but also enhanced their activation status. Pulmonary adaptive immune responses were characterized by the induction of a strongly Th17-polarized response. When compared with a mixture of soluble Ag with empty microcapsules, Ag encapsulation significantly enhanced the strength of this local mucosal response. Given their unique property to selectively generate Th17-polarized immune responses, PEMs may become of significant interest in the development of effective vaccines against fungal and bacterial species.
由于肺部的表面积较大，因此成为非侵入性疫苗传递的诱人途径，除了能够诱导全身免疫外，还有潜力诱导局部黏膜免疫反应。为了引发适应性免疫，抗原需要添加佐剂，佐剂不仅可以增强免疫反应的强度，还可以决定所引发的反应类型。在这项研究中，我们评估了由生物聚合物硫酸葡聚糖和聚 L-精氨酸组成的聚电解质微胶囊 (PEM) 的佐剂特性。PEM 形成了一类全新的微胶囊，它们是通过将带相反电荷的聚合物（聚电解质）顺序吸附到牺牲胶体模板上而产生的，然后溶解该模板，留下一个空心微胶囊，其周围有一层薄壳。经气管内滴注后，PEM 不仅被 APC 有效摄取，而且增强了它们的激活状态。肺部适应性免疫反应的特征是诱导强烈的 Th17 极化反应。与含有空微胶囊的可溶性 Ag 混合物相比，Ag 包封显著增强了局部黏膜反应的强度。鉴于它们选择性地产生 Th17 极化免疫反应的独特特性，PEM 在开发针对真菌和细菌的有效疫苗方面可能具有重要意义。
