1 / 26

Vaccination against allergy

Vaccination against allergy. Ulla Seppälä, PhD Vaccine Research. What is Allergy ?. sensitization. IgE- antibodies. X. Allergic response(s) Immediate-type Delayed- type. Non-IgE mediated hypersensitivity. CD23. B. IgE. APC. T-cell. HLA. -. class II. IgE. Mast cell. T-cell.

nysa
Download Presentation

Vaccination against allergy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Vaccination against allergy Ulla Seppälä, PhD Vaccine Research

  2. What is Allergy ? sensitization IgE- antibodies X • Allergic response(s) • Immediate-type • Delayed- type Non-IgE mediated hypersensitivity

  3. CD23 B IgE APC T-cell HLA - class II IgE Mast cell T-cell B-cell IgM/D Mediator release What is causing the symptoms ?- Sensitisation > < Clinical allergy - Allergens “other components” Andersson A-C, Seppälä U, Rudin A.Activation of human neonatal monocyte-derived dendritic cells by lipopolysaccharide: Down-regulation of birch allergen-induced Th2 responses. Eur J Immunol. 2004;34(12) :3516-24.

  4. Most common sources of inhalant allergens Phleum pratense Betula verrucosa Dermatophagoides pteronyssinus Felis domesticus

  5. Vespid & Bee venom allergens Apis mellifera Vespula vulgaris

  6. Allergens and Allergen Diagnostics Allergen Diagnostics: Clinical diagnosis In vitro: specific IgE In vivo: SPT / allergen extracts

  7. What is allergy vaccination? • Allergens are administered: in different doses • at different sites } ”the immune response is changed” - Allergy vaccination Tolerance Reaction - Allergen

  8. What is allergy vaccination ? Subcutaneous Immunotherpy /SCIT

  9. What is allergy vaccination ? Sublingual Immunotherapy / SLIT

  10. Allergen Specific Immunotherapy Anergy = clonal silence or actual clonal deletion of allergen-reactive T-cells Immunoregulation-induced immune deviation, leading into different cytokine milieu in a target tissue Induction a state of tolerance by utilizing T - lymphocytes as targets Rossenwasser LJ and Gelfand EW. Immunotherapy with antigens and epitopes. Am. J Repir.Cell. Mol. Biol. 1999:21;4-6.

  11. Proposed mechanisms in immunotherapy Tregs/ CD4+CD25+ IL-10/TGF-b Th2/Th1 Th2/Th1 SIT + IgG4 Till SJ et al.Mechanisms of immunotherapy. J Allergy Clin Immunol 2004;113:1025-34.

  12. Targeting the therapeutic tools ? Sensitisation Allergic Reaction T - helper - cell differentiation Late Phase Reaction + CD8 T - cells Allergen APC Cell mediated immunity g g IFN - IFN - IgG - production IL - 10 IL - 12 Eosinophil DTH Th1 - + g + IFN - a TNF - + + - g - Th0 - IL - 4 APC IL - 5 Immediate Reaction IL - 4 + + + Th2 PGE 2 IL - 4 APC IgE IL - 4 Mast cells and Basophils (IL - 13) Mast Cell B - cell Allergen

  13. What are the tools to cure allergy? CURRENT METHODS • natural allergen extracts • anti-allergy drugs e.g. antihistamines

  14. What are the tools to cure allergy? FUTURE METHODS DNA - vaccines rDNA - vaccines Reichert JM and Paquette. Therapeutic recombinant proteins: Trends in US approvals 1982 – 2002. Curr Opin Mol Ther. 2003:5;139-47.

  15. Therapeutical recombinant proteins / rDNAs allergen + CpG/ISS Fcg-Fel d 1 rIgs Daocheng Z et al.A chimeric human-cat fusion protein blocks cat-induced allergy. Nature Medicine 2005;11(4):446-49.

  16. Formulation of allergen vaccines by use of various adjuvants • Aluminium hydroxide • Bacterial origin mucosal adjuvants • CpG ODN, • Monophosphoryl lipid A (MPL) • Cholera toxin /CT (Vibrio cholera), entero toxin /LT (Escherichia coli) • Carbohydrates / (CBPs) • Microencapsulated allergen vaccines ”An adjuvant is an agent which, while not having any specific antigenic effect in itself, may stimulate the immune system, increasing the response to a vaccine.” Francis JN, Durham SR.Adjuvants for allergen immunotherapy: experimental results and clinical perspectives. Curr Opin Allergy Clin Immunol. 2004 Dec;4(6):543-8. Freytag LC, Clements JD.Mucosal adjuvants. Vaccine. 2005 Mar 7;23(15):1804-13.

  17. How to monitor allergen immunotherapy ? • improved clinical phenotype • serum IgE / IgG4 –levels IgE / IgG4 • decrease in number of mast cells and eosinophils after allergen provocation • modified and/or reduced production of cytokines • BIOMARKERS ? ! Walker C and Zuany-Amorim. New trends in immunotherapy to prevent atopic diseases. TRENDS Pharm Sci. 2001;22(2):84-90.

  18. How to monitor allergen immunotherapy ? A prequisite for a vaccine is the knowledge of how to induce Treg cells in vivo + DNA / protein arrays ”omics” technologies Sauer S et al.Miniaturization in functional genomics and proteomics. Nature Reviews Genetics. 2005;6:465-76.

  19. ”Genomics and proteomics of allergic disease” • Identification of thedisease genes; for design of new classes of anti-inflammatory compounds • Identification of expression and function of proteins; to obtain increased knowledge of mechanisms underlying allergic disease • Identifiction of novel biomarkers TODA M and ONO SJ.Genomics and proteomics of allergic disease. Immunol. 2002;106:1-10.

  20. Microarray technology • DNA – microarrays: • High – throughput analysis and expression of multiple genes or single nucleotide polymorphisms (SNIPs). Karp CL et al. Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma. Nat Immunol 2000;1:181-7. Miklos GL, Maleszka R.Microarray reality checks in the context of a complex disease. Nat Biotechnol. 2004 May;22(5):615-21.

  21. Microarray technology • Protein –microarrays: • examine the time course of cytokine secretion pattern by cell cultures, T- cells, DCs, Mast Cells / Basophils • examine expression profiles of cells expressing recombinant allergens Schweitzer B et al. Multiplexed protein profiling on microarrays by rolling-circle amplification. Nature Biotechnology, 2002;20:359-65.

  22. Proteomics technology • investigation of the influence of SNIPs in gene expression and function • of the proteins = elucidation of disease gene expression • transcriptome = proteome • follow-up of the Th1/Th2/Treg – profiles • – up / down regulation of signal transduction pathways, marker molecules • plasma / serum proteomics • characterization cellular responses against natural and/or modified rDNA Chromy BA et al. Proteomic Analysis of Human Serum by Two-Dimentional Differential Gel Electrophoresis after Depletion of High-Abundant Proteins. J Proteome Res. 2004;3:1120-1127.

  23. Proteomics in Allergy Research Fehninger T.E. etal. Exploring the context of lung proteome within the airway mucosa following allergen challenge. J Proteome Res. 2004;3:307-20.

  24. Identification of the disease genes or biomarkers pI MW Identification of the proteins / peptides by Mass Spectrometry DATABASE SEARCH Weingarten P et al. Application of proteomics and protein analysis for biomarker and target finding for immunotherapy. Methods Mol Med. 2005;109:155-74.

  25. Biomarker discovery: PEPTIDOMICS • Peptides are ideal candidates for biomarkers • Isolation/ measurement of biomarkers from blood - clinical application • Proteases liberate biomarkers – processing and specific degradation products – discovery tool ! • Hormones • Cytokines • Growth factors • etc. • Schulte I. et al. Peptides in body fluids and tissues as markers of disease. • Expert Rev Mol Diagn. 2005 Mar;5(2):145-57.

  26. Conclusions A B C D “New vaccines”

More Related