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基于凝胶相1,2-二硬脂酰-sn-甘油-3-磷酸胆碱的脂质体在增强树突状细胞上主要组织相容性复合体II类分子的抗原呈递和共刺激分子表达方面优于液相脂质体。

Gel Phase 1,2-Distearoyl--glycero-3-phosphocholine-Based Liposomes Are Superior to Fluid Phase Liposomes at Augmenting Both Antigen Presentation on Major Histocompatibility Complex Class II and Costimulatory Molecule Display by Dendritic Cells .

作者信息

Norling Karin, Bernasconi Valentina, Agmo Hernández Víctor, Parveen Nagma, Edwards Katarina, Lycke Nils Y, Höök Fredrik, Bally Marta

机构信息

Division of Biological Physics, Department of Physics , Chalmers University of Technology , 412 96 Gothenburg , Sweden.

Mucosal Immunobiology and Vaccine Center (MIVAC), Department of Microbiology and Immunology, Institute of Biomedicine , University of Gothenburg , 405 30 Gothenburg , Sweden.

出版信息

ACS Infect Dis. 2019 Nov 8;5(11):1867-1878. doi: 10.1021/acsinfecdis.9b00189. Epub 2019 Sep 24.

DOI:10.1021/acsinfecdis.9b00189
PMID:31498993
Abstract

Lipid-based nanoparticles have in recent years attracted increasing attention as pharmaceutical carriers. In particular, reports of them having inherent adjuvant properties combined with their ability to protect antigen from degradation make them suitable as vaccine vectors. However, the physicochemical profile of an ideal nanoparticle for vaccine delivery is still poorly defined. Here, we used an dendritic cell assay to assess the immunogenicity of a variety of liposome formulations as vaccine carriers and adjuvants. Using flow cytometry, we investigated liposome-assisted antigen presentation as well as the expression of relevant costimulatory molecules on the cell surface. Cytokine secretion was further evaluated with an enzyme-linked immunosorbent assay (ELISA). We show that liposomes can successfully enhance antigen presentation and maturation of dendritic cells, as compared to vaccine fusion protein (CTA1-3Eα-DD) administered alone. In particular, the lipid phase state of the membrane was found to greatly influence the vaccine antigen processing by dendritic cells. As compared to their fluid phase counterparts, gel phase liposomes were more efficient at improving antigen presentation. They were also superior at upregulating the costimulatory molecules CD80 and CD86 as well as increasing the release of the cytokines IL-6 and IL-1β. Taken together, we demonstrate that gel phase liposomes, while nonimmunogenic on their own, significantly enhance the antigen-presenting ability of dendritic cells and appear to be a promising way forward to improve vaccine immunogenicity.

摘要

近年来,基于脂质的纳米颗粒作为药物载体越来越受到关注。特别是,有报道称它们具有内在的佐剂特性,同时能够保护抗原不被降解,这使得它们适合作为疫苗载体。然而,用于疫苗递送的理想纳米颗粒的物理化学特性仍未明确界定。在此,我们使用树突状细胞试验来评估多种脂质体制剂作为疫苗载体和佐剂的免疫原性。通过流式细胞术,我们研究了脂质体辅助的抗原呈递以及细胞表面相关共刺激分子的表达。用酶联免疫吸附测定(ELISA)进一步评估细胞因子分泌。我们发现,与单独施用的疫苗融合蛋白(CTA1-3Eα-DD)相比,脂质体能够成功增强树突状细胞的抗原呈递和成熟。特别是,发现膜的脂质相状态对树突状细胞处理疫苗抗原的过程有很大影响。与处于流体相的脂质体相比,凝胶相脂质体在改善抗原呈递方面更有效。它们在上调共刺激分子CD80和CD86以及增加细胞因子IL-6和IL-1β的释放方面也更具优势。综上所述,我们证明凝胶相脂质体虽然自身无免疫原性,但能显著增强树突状细胞的抗原呈递能力,似乎是提高疫苗免疫原性的一个有前景的方向。

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