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肉苁蓉多糖功能化树枝状纤维纳米二氧化硅作为口服疫苗佐剂递送体,增强黏膜和系统免疫。

Cistanche deserticola polysaccharide-functionalized dendritic fibrous nano-silica as oral vaccine adjuvant delivery enhancing both the mucosal and systemic immunity.

机构信息

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.

Collage of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, PR China.

出版信息

Int J Biol Macromol. 2024 Mar;262(Pt 2):129982. doi: 10.1016/j.ijbiomac.2024.129982. Epub 2024 Feb 12.

DOI:10.1016/j.ijbiomac.2024.129982
PMID:38354941
Abstract

Oral vaccines are a safe and convenient alternative to injected vaccines and have great potential to prevent major infectious diseases. However, the harsh gastrointestinal (GI) environment, mucus barriers, low immunogenicity, and lack of effective and safe mucosal adjuvants are the major challenges for oral vaccine delivery. In recent years, nanoparticle-based strategies have become attractive for improving oral vaccine delivery. Here, the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) were prepared and investigated how to impact the immune responses. CDP-DFNS facilitated the antigen uptake in mouse bone marrow-derived dendritic cells (BMDCs), and induce the activation of DCs in vitro. Furthermore, in vivo experiments, the result showed that the uptake efficiency by Peyer's patches (PPs) of CDP-DFNS/BSA was the best. And CDP-DFNS/BSA then significantly activated the DCs in lamina propria (LP), and T/B cells in PPs and mesenteric lymph nodes (MLNs). Moreover, the memory T cell responses in later period of vaccination was stronger than other groups. In addition, CDP-DFNS/BSA enhanced BSA-specific antibody IgG, IgA production, and SIgA secretion, was effective at inducing a strong mixed Th1/Th2 response and mucosal antibody responses. These results indicated that CDP-DFNS deserves further consideration as an oral vaccine adjuvant delivery system.

摘要

口服疫苗是一种安全且方便的注射疫苗替代品,具有预防重大传染病的巨大潜力。然而,恶劣的胃肠道(GI)环境、黏液屏障、低免疫原性以及缺乏有效和安全的黏膜佐剂,这些都是口服疫苗传递的主要挑战。近年来,基于纳米粒子的策略已成为改善口服疫苗传递的有吸引力的方法。在这里,接枝有肉苁蓉多糖(CDP)的树突状纤维纳米硅(DFNS)纳米粒子(CDP-DFNS)被制备,并研究了其如何影响免疫反应。CDP-DFNS 促进了抗原在小鼠骨髓来源树突状细胞(BMDCs)中的摄取,并在体外诱导了 DC 的激活。此外,在体内实验中,结果表明 CDP-DFNS/BSA 的摄取效率最高。然后,CDP-DFNS/BSA 显著激活了固有层(LP)中的 DC 以及派尔集合淋巴结(PPs)和肠系膜淋巴结(MLNs)中的 T/B 细胞。此外,接种后后期的记忆 T 细胞反应比其他组更强。此外,CDP-DFNS/BSA 增强了 BSA 特异性抗体 IgG、IgA 的产生和 SIgA 的分泌,有效诱导了强烈的混合 Th1/Th2 反应和黏膜抗体反应。这些结果表明,CDP-DFNS 值得进一步考虑作为口服疫苗佐剂传递系统。

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