Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
Mol Pharm. 2021 Jun 7;18(6):2274-2284. doi: 10.1021/acs.molpharmaceut.1c00090. Epub 2021 Apr 30.
Nanoparticle vaccine delivery systems have been emerging strategies for inducing potent immune responses to prevent and treat infectious diseases and cancers. The properties of nanoparticle vaccine delivery systems, such as nanoparticle size, surface charge, and antigen release kinetics, have been extensively studied and proven to effectively influence the efficacy of vaccine responses. However, a few types of research have focused on the influence of administration routes of nanoparticle vaccines on immune responses. Herein, to investigate how the administration routes affect the immune responses of nanoparticles vaccines, we developed a nanoparticles system (NPs), in which the ovalbumin (OVA) and Angelica sinensis polysaccharide (ASP) were incorporated into poly(lactic--glycolic acid) (PLGA) nanoparticles and the polyethylenimine (PEI) was coated on the surface of nanoparticles. The NPs vaccine was intramuscularly and subcutaneously injected (im and sc) into mice, and the immune responses induced by these two delivery routes were compared. The results showed that both im and sc administration of NPs vaccines elicited strong antigen-specific IgG, IgG1, and IgG2a antibody responses, with no significant difference. In contrast, NP vaccines with sc administration significantly enhanced immune responses, such as enhancing the recruitment and activation of dendritic cells (DCs) in lymph nodes (LNs), promoting the antigen transport into draining lymph nodes, increasing the secretion of cytokines, improving the ratio of CD4T cells to CD8 T cells, activating cytotoxic T lymphocyte response, and inducing a strong cellular immune response. These results may provide a new insight onto the development of vaccine delivery systems.
纳米颗粒疫苗传递系统已成为诱导有效免疫反应以预防和治疗传染病和癌症的新兴策略。纳米颗粒疫苗传递系统的特性，如纳米颗粒大小、表面电荷和抗原释放动力学，已得到广泛研究，并被证明可有效影响疫苗反应的效果。然而，少数研究集中在纳米颗粒疫苗的给药途径对免疫反应的影响上。在此，为了研究给药途径如何影响纳米颗粒疫苗的免疫反应，我们开发了一种纳米颗粒系统（NPs），其中将卵清蛋白（OVA）和当归多糖（ASP）掺入聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒中，并在纳米颗粒表面涂覆聚亚乙基亚胺（PEI）。NPs 疫苗通过肌肉内和皮下注射（im 和 sc）到小鼠体内，并比较了这两种给药途径引起的免疫反应。结果表明，im 和 sc 给药途径均可引发强烈的抗原特异性 IgG、IgG1 和 IgG2a 抗体反应，无显著差异。相比之下，sc 给药的 NP 疫苗显著增强了免疫反应，如增强淋巴结（LN）中树突状细胞（DC）的募集和激活，促进抗原向引流淋巴结的转运，增加细胞因子的分泌，提高 CD4T 细胞与 CD8T 细胞的比例，激活细胞毒性 T 淋巴细胞反应，并诱导强烈的细胞免疫反应。这些结果可能为疫苗传递系统的开发提供新的思路。
