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在未致敏和致敏 BALB/c 小鼠中 Asp f1 表位的预防和治疗潜力。

Prophylactic and Therapeutic Potential of Asp f1 Epitopes in Naïve and Sensitized BALB/c Mice.

机构信息

Institute of Genomics and Integrative Biology, Mall Road, Delhi, India.

出版信息

Immune Netw. 2009 Oct;9(5):179-91. doi: 10.4110/in.2009.9.5.179. Epub 2009 Oct 30.

DOI:10.4110/in.2009.9.5.179
PMID:20157606
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2816952/
Abstract

BACKGROUND

The present study examines a hypothesis that short allergen-derived peptides may shift an Aspergillus fumigatus (Afu-) specific TH2 response towards a protective TH1. Five overlapping peptides (P1-P5) derived from Asp f1, a major allergen/antigen of Afu, were evaluated for prophylactic or therapeutic efficacy in BALB/c mice.

METHODS

To evaluate the prophylactic efficacy, peptides were intranasally administered to naïve mice and challenged with Afu-allergens/antigens. For evaluation of therapeutic efficacy, the mice were sensitized with Afu-allergens/antigens followed by intranasal administration of peptides. The groups were compared for the levels of Afu-specific antibodies in sera and splenic cytokines evaluated by ELISA. Eosinophil peroxidase activity was examined in the lung cell suspensions and lung inflammation was assessed by histopathogy.

RESULTS

Peptides P1-, P2- and P3 decreased Afu-specific IgE (84.598.9%) and IgG antibodies (45.771.6%) in comparison with Afu-sensitized mice prophylactically. P1- and P2-treated ABPA mice showed decline in Afu-specific IgE (76.488%) and IgG antibodies (1554%). Increased IgG2a/IgG1 and IFN-gamma/IL-4 ratios were observed. P1-P3 prophylactically and P1 therapeutically decreased IL-5 levels and eosinophil peroxidase activity. P1 decreased inflammatory cells' infiltration in lung tissue comparable to non-challenged control.

CONCLUSION

Asp f1-derived peptide P1, prophylactically and therapeutically administered to Balb/c mice, is effective in regulating allergic response to allergens/antigens of Afu, and may be explored for immunotherapy of allergic aspergillosis in humans.

摘要

背景

本研究检验了一个假设，即短过敏原衍生肽可能会将烟曲霉（Afu）特异性 TH2 反应转向保护性 TH1。从 Afu 的主要过敏原/抗原 Asp f1 中衍生出的 5 个重叠肽（P1-P5）被评估用于 BALB/c 小鼠的预防或治疗功效。

方法

为了评估预防功效，将肽经鼻内给予新生小鼠，并与 Afu 过敏原/抗原进行挑战。为了评估治疗功效，用 Afu 过敏原/抗原对小鼠进行敏化，然后经鼻内给予肽。通过 ELISA 评估血清中 Afu 特异性抗体水平和脾细胞因子，比较各组。在肺细胞悬浮液中检查嗜酸性粒细胞过氧化物酶活性，并通过组织病理学评估肺炎症。

结果

与 Afu 致敏的预防性小鼠相比，肽 P1、P2 和 P3 降低了 Afu 特异性 IgE（84.598.9%）和 IgG 抗体（45.771.6%）。P1 和 P2 治疗的 ABPA 小鼠显示 Afu 特异性 IgE（76.488%）和 IgG 抗体（1554%）下降。观察到 IgG2a/IgG1 和 IFN-γ/IL-4 比值增加。P1-P3 预防性和 P1 治疗性地降低了 IL-5 水平和嗜酸性粒细胞过氧化物酶活性。P1 降低了肺组织中炎症细胞的浸润，与未受挑战的对照组相当。

结论

Asp f1 衍生肽 P1，预防性和治疗性地给予 Balb/c 小鼠，可有效调节对 Afu 过敏原/抗原的过敏反应，可用于人类变应性曲霉病的免疫治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/ce54e194a7c1/in-9-179-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/c943c1bd34fe/in-9-179-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/3c7807a27e5a/in-9-179-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/d989cc638023/in-9-179-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/a73d59206e83/in-9-179-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/7f099a71fac4/in-9-179-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/ce54e194a7c1/in-9-179-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/c943c1bd34fe/in-9-179-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/3c7807a27e5a/in-9-179-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/d989cc638023/in-9-179-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/7f099a71fac4/in-9-179-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1c7/2816952/ce54e194a7c1/in-9-179-g006.jpg

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