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

  • Received : 2009.07.21
  • Accepted : 2009.09.04
  • Published : 2009.10.31
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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 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-${\gamma}$/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.

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References

  1. Tillie-Leblond I, Tonnel AB: Allergic bronchopulmonary aspergillosis. Allergy 60;1004-1013, 2005 https://doi.org/10.1111/j.1398-9995.2005.00887.x
  2. Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, Denning DW, Crameri R, Brody AS, Light M, Skov M, Maish W, Mastella G: Participants in the Cystic Fibrosis Foundation Consensus Conference: Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 37(Suppl 3);S225-S264, 2003 https://doi.org/10.1086/376525
  3. Zander DS: Allergic bronchopulmonary aspergillosis: an overview. Arch Pathol Lab Med 129;924-928, 2005
  4. Eaton T, Garrett J, Milne D, Frankel A, Wells AU: Allergic bronchopulmonary aspergillosis in the asthma clinic. A prospective evaluation of CT in the diagnostic algorithm. Chest 118;66-72, 2000 https://doi.org/10.1378/chest.118.1.66
  5. Larche M, Akdis CA, Valenta R: Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol 6; 761-771, 2006 https://doi.org/10.1038/nri1934
  6. Akdis M, Akdis CA: Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol 119;780-791, 2007 https://doi.org/10.1016/j.jaci.2007.01.022
  7. Ajduk J, Marinic I, Aberle N, Rabatic S, Gagro A: Effect of house dust mite immunotherapy on transforming growth factor beta1-producing T cells in asthmatic children. Ann Allergy Asthma Immunol 100;314-323, 2008 https://doi.org/10.1016/S1081-1206(10)60592-3
  8. Pfaar O, Klimek L: Anaphylaxis--life-threatening allergic reactions. MMW Fortschr Med 150;35-39, 2008
  9. Pfaar O, Klimek L: Efficacy and safety of specific immunotherapy with a high-dose sublingual grass pollen preparation: a double-blind, placebo-controlled trial. Ann Allergy Asthma Immunol 100;256-263, 2008 https://doi.org/10.1016/S1081-1206(10)60451-6
  10. Senti G, Johansen P, Martinez Gomez J, Prinz Varicka BM, Kundig TM: Efficacy and safety of allergen-specific immunotherapy in rhinitis, rhinoconjunctivitis, and bee/wasp venom allergies. Int Rev Immunol 24;519-531, 2005 https://doi.org/10.1080/08830180500370944
  11. Akdis CA, Akdis M: Mechanisms and treatment of allergic disease in the big picture of regulatory T cells. J Allergy Clin Immunol 123;735-746, 2009 https://doi.org/10.1016/j.jaci.2009.02.030
  12. Lizaso MT, Tabar AI, Garcia BE, Gomez B, Algorta J, Asturias JA, Martinez A: Double-blind, placebo-controlled Alternaria alternata immunotherapy: in vivo and in vitro parameters. Pediatr Allergy Immunol 19;76-81, 2008
  13. Malling HJ, Djurup R: Diagnosis and immunotherapy of mould allergy. VII. IgG subclass response and relation to the clinical efficacy of immunotherapy with Cladosporium. Allergy 43;60-70, 1988 https://doi.org/10.1111/j.1398-9995.1988.tb02045.x
  14. Tabar AI, Lizaso MT, Garcia BE, Gomez B, Echechipia S, Aldunate MT, Madariaga B, Martinez A: Double-blind, placebo-controlled study of Alternaria alternata immunotherapy: clinical efficacy and safety. Pediatr Allergy Immunol 19;67-75, 2008
  15. Chauhan B, Knutsen A, Hutcheson PS, Slavin RG, Bellone CJ: T cell subsets, epitope mapping, and HLA-restriction in patients with allergic bronchopulmonary aspergillosis. J Clin Invest 97;2324-2331, 1996 https://doi.org/10.1172/JCI118675
  16. Kurup VP, Banerjee B, Murali PS, Greenberger PA, Krishnan M, Hari V, Fink JN: Immunodominant peptide epitopes of allergen, Asp f1 from the fungus Aspergillus fumigatus. Peptides 19;1469-1477, 1998 https://doi.org/10.1016/S0196-9781(98)00113-2
  17. Madan T, Arora N, Sarma PU: Ribonuclease activity dependent cytotoxicity of Asp fl, a major allergen of A. fumigatus. Mol Cell Biochem 175;21-27, 1997 https://doi.org/10.1023/A:1006822906343
  18. Madan T, Arora N, Sarma PU: Identification and evaluation of a major cytotoxin of A. fumigatus. Mol Cell Biochem 167;89-97, 1997 https://doi.org/10.1023/A:1006823706119
  19. Madan T, Priyadarsiny P, Vaid M, Kamal N, Shah A, Haq W, Katti SB, Sarma PU: Use of a synthetic peptide epitope of Asp f1, a major allergen or antigen of Aspergillus fumigatus, for improved immunodiagnosis of allergic broncho-pulmonary aspergillosis. Clin Diagn Lab Immunol 11;552-558, 2004
  20. Ramadan G, Davies B, Kurup VP, Keever-Taylor CA: Generation of cytotoxic T cell responses directed to human leucocyte antigen Class I restricted epitopes from the Aspergillus f16 allergen. Clin Exp Immunol 140;81-91, 2005 https://doi.org/10.1111/j.1365-2249.2005.02738.x
  21. Ramadan G, Davies B, Kurup VP, Keever-Taylor CA: Generation of Th1 T cell responses directed to a HLA Class II restricted epitope from the Aspergillus f16 allergen. Clin Exp Immunol 139;257-267, 2005 https://doi.org/10.1111/j.1365-2249.2005.02699.x
  22. Svirshchevskaya EV, Alekseeva LG, Titov VM, Frolova EG, Sapozhnikov AM: Determination of T and B Cell Epitopes of Aspergillus fumigatus Ribotoxin and Heat Shock Protein. Russ J Immunol 3;61-68, 1998
  23. Arruda LK, Mann BJ, Chapman MD: Selective expression of a major allergen and cytotoxin, Asp f I, in Aspergillus fumigatus. Implications for the immunopathogenesis of Aspergillus-related diseases. J Immunol 149;3354-3359, 1992
  24. Moser M, Crameri R, Menz G, Schneider T, Dudler T, Virchow C, Gmachl M, Blaser K, Suter M: Cloning and expression of recombinant Aspergillus fumigatus allergen I/a (rAsp f I/a) with IgE binding and type I skin test activity. J Immunol 149;454-460, 1992
  25. Kamal N, Chowdhury S, Madan T, Sharma D, Attreyi M, Haq W, Katti SB, Kumar A, Sarma PU: Tryptophan residue is essential for immunoreactivity of a diagnostically relevant peptide epitope of A. fumigatus. Mol Cell Biochem 275; 223-231, 2005 https://doi.org/10.1007/s11010-005-2056-x
  26. Svirshchevskaya E, Frolova E, Alekseeva L, Kotzareva O, Kurup VP: Intravenous injection of major and cryptic peptide epitopes of ribotoxin, Asp f1 inhibits T cell response induced by crude Aspergillus fumigatus antigens in mice. Peptides 21;1-8, 2000 https://doi.org/10.1016/S0196-9781(99)00173-4
  27. Bhasin M, Raghava GP: SVM based method for predicting HLA-DRB* 0401 binding peptides in an antigen sequence. Bioinformatics 20;421-423, 2004 https://doi.org/10.1093/bioinformatics/btg424
  28. Zhang GL, Srinivasan KN, Veeramani A, August JT, Brusic V: PREDBALB/c: a system for the prediction of peptide binding to H2d molecules, a haplotype of the BALB/c mouse. Nucleic Acids Res 33;W180-W183, 2005 https://doi.org/10.1093/nar/gki479
  29. Bhasin M, Raghava GP: Prediction of CTL epitopes using QM, SVM and ANN techniques. Vaccine 22;3195-3204, 2004 https://doi.org/10.1016/j.vaccine.2004.02.005
  30. Madan T, Kishore U, Singh M, Strong P, Clark H, Hussain EM, Reid KB, Sarma PU: Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. J Clin Invest 107;467-475, 2001 https://doi.org/10.1172/JCI10124
  31. Astori M, von Garnier C, Kettner A, Dufour N, Corradin G, Spertini F: Inducing tolerance by intranasal administration of long peptides in naive and primed CBA/J mice. J Immunol 165;3497-3505, 2000 https://doi.org/10.4049/jimmunol.165.6.3497
  32. Hall G, Houghton CG, Rahbek JU, Lamb JR, Jarman ER: Suppression of allergen reactive Th2 mediated responses and pulmonary eosinophilia by intranasal administration of an immunodominant peptide is linked to IL-10 production. Vaccine 21;549-561, 2003 https://doi.org/10.1016/S0264-410X(02)00394-8
  33. Nigam S, Ghosh PC, Sarma PU: Altered immune response to liposomal allergens of Aspergillus fumigatus in mice. Int J Pharm 236;97-109, 2002 https://doi.org/10.1016/S0378-5173(02)00013-3
  34. Boyum A: Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl 97;77-89, 1968
  35. Alexander C, Ying S, B Kay A, Larche M: Fel d 1-derived T cell peptide therapy induces recruitment of CD4+ CD25+; CD4+ interferon-gamma+ T helper type 1 cells to sites of allergen-induced late-phase skin reactions in cat-allergic subjects. Clin Exp Allergy 35;52-58, 2005 https://doi.org/10.1111/j.1365-2222.2005.02143.x
  36. Hoyne GF, O'Hehir RE, Wraith DC, Thomas WR, Lamb JR: Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of the dominant T cell epitope in naive and sensitized mice. J Exp Med 178;1783-1788, 1993 https://doi.org/10.1084/jem.178.5.1783
  37. Kay AB, Larche M: Allergen immunotherapy with cat allergen peptides. Springer Semin Immunopathol 25;391-399, 2004 https://doi.org/10.1007/s00281-003-0146-y
  38. Yoshitomi T, Nakagami Y, Hirahara K, Taniguchi Y, Sakaguchi M, Yamashita M: Intraoral administration of a T-cell epitope peptide induces immunological tolerance in Cry j 2-sensitized mice. J Pept Sci 13;499-503, 2007 https://doi.org/10.1002/psc.869
  39. Helbling A, Reimers A: Immunotherapy in fungal allergy. Curr Allergy Asthma Rep 3;447-453, 2003 https://doi.org/10.1007/s11882-003-0082-x
  40. Crameri R, Weichel M, Fluckiger S, Glaser AG, Rhyner C: Fungal allergies: a yet unsolved problem. Chem Immunol Allergy 91;121-133, 2006
  41. Simon-Nobbe B, Denk U, Poll V, Rid R, Breitenbach M: The spectrum of fungal allergy. Int Arch Allergy Immunol 145;58-86, 2008 https://doi.org/10.1159/000107578
  42. Finkelman FD, Katona IM, Mosmann TR, Coffman RL: IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol 140;1022-1027, 1988
  43. Kozutsumi D, Tsunematsu M, Yamaji T, Murakami R, Yokoyama M, Kino K: Cry-consensus peptide, a novel peptide for immunotherapy of Japanese cedar pollinosis, induces Th1-predominant response in Cry j 1-sensitized B10.S mice. Biol Pharm Bull 29;2506-2509, 2006 https://doi.org/10.1248/bpb.29.2506
  44. von Garnier C, Astori M, Kettner A, Dufour N, Heusser C, Corradin G, Spertini F: Allergen-derived long peptide immunotherapy down-regulates specific IgE response and protects from anaphylaxis. Eur J Immunol 30;1638-1645, 2000 https://doi.org/10.1002/1521-4141(200006)30:6<1638::AID-IMMU1638>3.0.CO;2-R
  45. Furin MJ, Norman PS, Creticos PS, Proud D, Kagey-Sobotka A, Lichtenstein LM, Naclerio RM: Immunotherapy decreases antigen-induced eosinophil cell migration into the nasal cavity. J Allergy Clin Immunol 88;27-32, 1991 https://doi.org/10.1016/0091-6749(91)90297-2
  46. Rak S, Lowhagen O, Venge P: The effect of immunotherapy on bronchial hyperresponsiveness and eosinophil cationic protein in pollen-allergic patients. J Allergy Clin Immunol 82;470-480, 1988 https://doi.org/10.1016/0091-6749(88)90021-8
  47. Hamelmann E, Wahn U, Gelfand EW: Role of the Th2 cytokines in the development of allergen-induced airway inflammation and hyperresponsiveness. Int Arch Allergy Immunol 118;90-94, 1999 https://doi.org/10.1159/000024037
  48. Kurup VP, Murali PS, Guo J, Choi H, Banerjee B, Fink JN, Coffman RL: Anti-interleukin (IL)-4 and -IL-5 antibodies downregulate IgE and eosinophilia in mice exposed to Aspergillus antigens. Allergy 52;1215-1221, 1997 https://doi.org/10.1111/j.1398-9995.1997.tb02526.x
  49. Romani L: Immunity to fungal infections. Nat Rev Immunol 4;1-23, 2004 https://doi.org/10.1038/nri1290
  50. Bettelli E, Kuchroo VK: IL-12- and IL-23-induced T helper cell subsets: birds of the same feather flock together. J Exp Med 201;169-171, 2005 https://doi.org/10.1084/jem.20042279
  51. Jutel M, Klunker S, Akdis M, Malolepszy J, Thomet OA, Zak-Nejmark T, Blaser K, Akdis CA: Histamine upregulates Th1 and downregulates Th2 responses due to different patterns of surface histamine 1 and 2 receptor expression. Int Arch Allergy Immunol 124;190-192, 2001 https://doi.org/10.1159/000053707
  52. Jutel M, Watanabe T, Klunker S, Akdis M, Thomet OA, Malolepszy J, Zak-Nejmark T, Koga R, Kobayashi T, Blaser K, Akdis CA: Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature 413;420-425, 2001 https://doi.org/10.1038/35096564
  53. Johansen P, Senti G, Maria Martinez Gomez J, Kundig TM: Medication with antihistamines impairs allergen-specific immunotherapy in mice. Clin Exp Allergy 38;512-519, 2008 https://doi.org/10.1111/j.1365-2222.2007.02904.x
  54. Jutel M, Blaser K, Akdis CA: Histamine receptors in immune regulation and allergen-specific immunotherapy. Immunol Allergy Clin North Am 26;245-259, 2006 https://doi.org/10.1016/j.iac.2006.02.006
  55. Mehra NK, Verduijn W, Taneja V, Drabbels J, Singh SP, Giphart MJ: Analysis of HLA-DR2-associated polymorphisms by oligonucleotide hybridization in an Asian Indian population. Hum Immunol 32;246-253, 1991 https://doi.org/10.1016/0198-8859(91)90087-P
  56. Texier C, Pouvelle S, Busson M, Herve M, Charron D, Menez A, Maillere B: HLA-DR restricted peptide candidates for bee venom immunotherapy. J Immunol 164;3177-3184, 2000 https://doi.org/10.4049/jimmunol.164.6.3177

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