KMID : 0923620090090050179
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Immune Network 2009 Volume.9 No. 5 p.179 ~ p.191
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Prophylactic and Therapeutic Potential of Asp f1 Epitopes in Naive and Sensitized BALB/c Mice
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Chaudhary NeelRanmal
Mahajan Lakshna Madan Taruna Kumar Anil Raghava Gajendra Pratap Singh Katt Seturam Bandacharya
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Abstract
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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 naive 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 (84.5¡ 98.9%) and IgG antibodies (45.7¡71.6%) in comparison with Afu-sensitized mice prophylactically. P1- and P2-treated ABPA mice showed decline in Afu-specific IgE (76.4¡88%) and IgG antibodies (15¡54%). Increased IgG2a/IgG1 and IFN-?/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.
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KEYWORD
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Aspergillus fumigatus, allergic bronchopulmonary aspergillosis, Asp f1 peptides, cytokines, eosinophil, T helper cell
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