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负载粒细胞-巨噬细胞集落刺激因子的壳聚糖水凝胶作为免疫佐剂可增强抗原特异性免疫反应并降低毒性。

GM-CSF-loaded chitosan hydrogel as an immunoadjuvant enhances antigen-specific immune responses with reduced toxicity.

作者信息

Noh Kyung Hee, Park Yeong Min, Kim Hyuk Soon, Kang Tae Heung, Song Kwon-Ho, Lee Young-Ho, Byeon Yeongseon, Jeon Hat Nim, Jung In Duk, Shin Byung Cheol, Lee Kyung-Mi, Seong Seung-Yong, Han Hee Dong, Kim Tae Woo

机构信息

Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Gojan-1 Dong, Ansan-Si 425-707, Gyeonggi-Do, South Korea.

出版信息

BMC Immunol. 2014 Oct 18;15:48. doi: 10.1186/s12865-014-0048-x.

DOI:10.1186/s12865-014-0048-x
PMID:25323934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4201920/
Abstract

BACKGROUND

The application of vaccine adjuvants has been vigorously studied for a diverse range of diseases in order to improve immune responses and reduce toxicity. However, most adjuvants have limited uses in clinical practice due to their toxicity.

METHODS

Therefore, to reduce health risks associated with the use of such adjuvants, we developed an advanced non-toxic adjuvant utilizing biodegradable chitosan hydrogel (CH-HG) containing ovalbumin (OVA) and granulocyte-macrophage colony-stimulating factor (GM-CSF) as a local antigen delivery system.

RESULTS

After subcutaneous injection into mice, OVA/GM-CSF-loaded CH-HG demonstrated improved safety and enhanced OVA-specific antibody production compared to oil-based adjuvants such as Complete Freund's adjuvant (CFA) or Incomplete Freund's adjuvant (IFA). Moreover, CH-HG system-mediated immune responses was characterized by increased number of OVA-specific CD4(+) and CD8(+) INF-γ(+) T cells, leading to enhanced humoral and cellular immunity.

CONCLUSIONS

In this study, the improved safety and enhanced immune response characteristics of our novel adjuvant system suggest the possibility of the extended use of adjuvants in clinical practice with reduced apprehension about toxic side effects.

摘要

背景

为了提高免疫反应并降低毒性,疫苗佐剂已针对多种疾病展开了深入研究。然而,大多数佐剂由于其毒性,在临床实践中的应用有限。

方法

因此,为降低使用此类佐剂带来的健康风险,我们开发了一种先进的无毒佐剂,它利用含有卵清蛋白(OVA)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的可生物降解壳聚糖水凝胶(CH-HG)作为局部抗原递送系统。

结果

皮下注射到小鼠体内后,与油基佐剂如完全弗氏佐剂(CFA)或不完全弗氏佐剂(IFA)相比,负载OVA/GM-CSF的CH-HG显示出更高的安全性,并增强了OVA特异性抗体的产生。此外,CH-HG系统介导的免疫反应表现为OVA特异性CD4(+)和CD8(+) INF-γ(+) T细胞数量增加,从而增强了体液免疫和细胞免疫。

结论

在本研究中,我们新型佐剂系统具有更高的安全性和增强的免疫反应特性,这表明在临床实践中扩大佐剂的使用范围并减少对毒副作用的担忧是有可能的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa98/4201920/ba7dbc8e68e1/12865_2014_48_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa98/4201920/46fd8e8998c7/12865_2014_48_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa98/4201920/4d20ce8bca3d/12865_2014_48_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa98/4201920/e10ca57522c5/12865_2014_48_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa98/4201920/ba7dbc8e68e1/12865_2014_48_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa98/4201920/46fd8e8998c7/12865_2014_48_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa98/4201920/4d20ce8bca3d/12865_2014_48_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa98/4201920/e10ca57522c5/12865_2014_48_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa98/4201920/ba7dbc8e68e1/12865_2014_48_Fig4_HTML.jpg

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