Center for Research in Molecular Medicine and Chronic Diseases, Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Santiago de Compostela 15706, Spain.
Nantes Université, CNRS, Unité des Sciences Biologiques et des Biotechnologies (US2B), UMR 6286, Nantes F-44000, France.
Bioconjug Chem. 2023 Sep 20;34(9):1563-1575. doi: 10.1021/acs.bioconjchem.3c00252. Epub 2023 Sep 11.
Pneumococcal conjugate vaccines offer an excellent safety profile and high protection against the serotypes comprised in the vaccine. However, inclusion of protein antigens fromcombined with potent adjuvants and a suitable delivery system are expected to both extend protection to serotype strains not represented in the formulation and stimulate a broader immune response, thus more effective in young children, elderly, and immunocompromised populations. Along this line, nanoparticle (NP) delivery systems can enhance the immunogenicity of antigens by protecting them from degradation and increasing their uptake by antigen-presenting cells, as well as offering co-delivery with adjuvants. We report herein the encapsulation of a semisynthetic glycoconjugate (GC) composed of a synthetic tetrasaccharide mimicking the serotype 14 capsular polysaccharide (CP14) linked to the Pneumococcal surface protein A (PsaA) using chitosan NPs (CNPs). These GC-loaded chitosan nanoparticles (GC-CNPs) were not toxic to human monocyte-derived dendritic cells (MoDCs), showed enhanced uptake, and displayed better immunostimulatory properties in comparison to the naked GC. A comparative study was carried out in mice to evaluate the immune response elicited by the glycoconjugate-administered subcutaneously (SC), where the GC-CNPs displayed 100-fold higher IgG response as compared with the group treated with nonencapsulated GC. Overall, the study demonstrates the potential of this chitosan-based nanovaccine for efficient delivery of glycoconjugate antigens.
肺炎球菌结合疫苗具有出色的安全性和针对疫苗所含血清型的高度保护作用。然而，将蛋白抗原与有效的佐剂和合适的传递系统结合使用，有望将保护作用扩展到疫苗配方中未包含的血清型菌株，并刺激更广泛的免疫反应，从而在幼儿、老年人和免疫功能低下人群中更有效。沿着这条线，纳米颗粒 (NP) 传递系统可以通过保护抗原免受降解和增加抗原呈递细胞的摄取，以及与佐剂共同传递，来提高抗原的免疫原性。我们在此报告了使用壳聚糖 NPs (CNPs) 封装由合成四糖模拟血清型 14 荚膜多糖 (CP14) 连接到肺炎球菌表面蛋白 A (PsaA) 的半合成糖缀合物 (GC)。与裸露的 GC 相比，这些负载 GC 的壳聚糖纳米颗粒 (GC-CNPs) 对人单核细胞衍生树突状细胞 (MoDCs) 没有毒性，显示出增强的摄取，并显示出更好的免疫刺激特性。在小鼠中进行了比较研究，以评估皮下 (SC) 给予糖缀合物引起的免疫反应，其中 GC-CNPs 与未包裹 GC 组相比，IgG 反应高 100 倍。总体而言，该研究证明了这种基于壳聚糖的纳米疫苗在有效递送糖缀合物抗原方面的潜力。
