Institute of Genomics and Integrative Biology, Mall Road, Delhi, India.
Immune Netw. 2009 Oct;9(5):179-91. doi: 10.4110/in.2009.9.5.179. Epub 2009 Oct 30.
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.
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.
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.
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.
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。
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。
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。
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。