利用抗坏血酸棕榈酸酯自组装形成的纳米结构改善亚单位疫苗的生物分布并增强其免疫反应。

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-05-06 DOI:10.1016/j.nano.2024.102749
Constanza Marin PhD , Federico N. Ruiz Moreno Pharmacist , María F. Sánchez Vallecillo PhD , María M. Pascual PhD , Nicolas D. Dho Biochemist , Daniel A. Allemandi PhD , Santiago D. Palma PhD , María C. Pistoresi-Palencia PhD , María I. Crespo PhD , Cesar G. Gomez PhD , Gabriel Morón PhD , Belkys A. Maletto PhD
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引用次数: 0

摘要

需要新的佐剂策略来提高基于蛋白质的亚单位疫苗的免疫原性。我们研究了使用 6-O- 抗坏血酸棕榈酸酯纳米结构配制卵清蛋白(OVA)蛋白和寡核苷酸(CpG-ODN)(OCC)的可能性。对小鼠进行单剂量免疫后,OCC 引起的 OVA 特异性免疫反应优于 OVA/CpG-ODN 溶液(OC)。流变学研究证明了 OCC 的自组装粘弹性能。生物分布研究表明,OCC 延长了 OVA 和 CpG-ODN 在注射部位和淋巴结的保留时间,减少了全身扩散。流式细胞计数测定表明,OCC 促进了 Ly6ChiCD11bhiCD11c + 单核细胞对 OVA 和 CpG-ODN 的共同吸收。OCC 和 OC 在淋巴结中诱导早期 IFN-γ,但 OCC 的浓度更高。相反,与用 OCC 免疫的小鼠相比,用 OC 免疫的小鼠血清 IFN-γ 浓度更高。在用 OCC 免疫的小鼠中,NK1.1+ 细胞是 IFN-γ 的主要产生者,IFN-γ 对 OVA 特异性 IgG2c 的转换至关重要。这些发现说明了这种纳米结构是如何改善疫苗反应的。
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Improved biodistribution and enhanced immune response of subunit vaccine using a nanostructure formed by self-assembly of ascorbyl palmitate

New adjuvant strategies are needed to improve protein-based subunit vaccine immunogenicity. We examined the potential to use nanostructure of 6-O-ascorbyl palmitate to formulate ovalbumin (OVA) protein and an oligodeoxynucleotide (CpG-ODN) (OCC). In mice immunized with a single dose, OCC elicited an OVA-specific immune response superior to OVA/CpG-ODN solution (OC). Rheological studies demonstrated OCC's self-assembling viscoelastic properties. Biodistribution studies indicated that OCC prolonged OVA and CpG-ODN retention at injection site and lymph nodes, reducing systemic spread. Flow-cytometry assays demonstrated that OCC promoted OVA and CpG-ODN co-uptake by Ly6ChiCD11bhiCD11c+ monocytes. OCC and OC induced early IFN-γ in lymph nodes, but OCC led to higher concentration. Conversely, mice immunized with OC showed higher serum IFN-γ concentration compared to those immunized with OCC. In mice immunized with OCC, NK1.1+ cells were the IFN-γ major producers, and IFN-γ was essential for OVA-specific IgG2c switching. These findings illustrate how this nanostructure improves vaccine's response.

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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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