Journal Mobile Options
Table of Contents
Vol. 150, No. 1, 2009
Issue release date: August 2009
Int Arch Allergy Immunol 2009;150:59–65
(DOI:10.1159/000210381)

Intralymphatic Injections as a New Administration Route for Allergen-Specific Immunotherapy

Martínez-Gómez J.M. · Johansen P. · Erdmann I. · Senti G. · Crameri R. · Kündig T.M.
aUnit for Experimental Immunotherapy, Department of Dermatology, University Hospital of Zurich, Zurich, and bSwiss Institute of Allergy and Asthma Research, Davos, Switzerland

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Background: IgE-mediated allergy can be treated by subcutaneous allergen-specific immunotherapy (SIT). However, the percentage of allergic patients undergoing SIT is low, mainly due to the long duration of the therapy and the risk of severe systemic allergic reactions associated with the allergen administration. To improve the safety and attractiveness of SIT for patients, alternative routes of allergen administration are being explored, such as sub-lingual or oral administration. Methods: The present study evaluated direct intralymphatic allergen administration as a means to enhance SIT with bee venom and cat fur allergens in mice. Allergen-specific antibody and T-cell responses were analysed by ELISA and flow cytometry. The therapeutic potential of intralymphatic immunisation in sensitised mice was analysed using an anaphylaxis model. Results: Direct injection of the major bee venom allergen phospholipase A2 or the major cat fur allergen Fel d 1 into inguinal lymph nodes enhanced allergen-specific IgG and T-cell responses when compared with subcutaneous injections. Moreover, only intralymphatic immunisation stimulated the production of the Th1-dependent subclass IgG2a, which is associated with improved protection against allergen-induced anaphylaxis. Biodistribution studies showed that injection into the lymph node delivered antigen more efficiently to subcutaneous lymph nodes than subcutaneous injection. Conclusions: As intralymphatic immunisation induced more than 10-fold higher IgG2a responses with 100-fold lower allergen doses than subcutaneous immunisation, this approach should allow to reduce both the number of allergen injections as well as the allergen dose, improving both efficacy and safety of SIT.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Bousquet J, Lockey R, Malling HJ: Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol 1998;102:558–562.
  2. Casale TB: Status of immunotherapy: current and future. J Allergy Clin Immunol 2004;113:1036–1039.
  3. Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O: Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol 2005;116:608–613.
  4. Larche M: Update on the current status of peptide immunotherapy. J Allergy Clin Immunol 2007;119:906–909.
  5. Riemer A, Scheiner O, Jensen-Jarolim E: Allergen mimotopes. Methods 2004;32:321–327.
  6. Creticos PS, Chen YH, Schroeder JT: New approaches in immunotherapy: allergen vaccination with immunostimulatory DNA. Immunol Allergy Clin North Am 2004;24:569–581, v.
  7. Johansen P, Senti G, Martinez Gomez JM, Storni T, von Beust BR, Wuthrich B, Bot A, Kundig TM: Toll-like receptor ligands as adjuvants in allergen-specific immunotherapy. Clin Exp Allergy 2005;35:1591–1598.
  8. Santeliz JV, Nest GV, Traquina P, Larsen E, Wills-Karp M: Amb a 1-linked CpG oligodeoxynucleotides reverse established airway hyperresponsiveness in a murine model of asthma. J Allergy Clin Immunol 2002;109:455–462.
  9. Jilek S, Walter E, Merkle HP, Corthesy B: Modulation of allergic responses in mice by using biodegradable poly(lactide-co-glycolide) microspheres. J Allergy Clin Immunol 2004;114:943–950.
  10. Kundig TM, Senti G, Schnetzler G, Wolf C, Prinz Vavricka BM, Fulurija A, Hennecke F, Sladko K, Jennings GT, Bachmann MF: Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults. J Allergy Clin Immunol 2006;117:1470–1476.
  11. Martinez Gomez JM, Fischer S, Csaba N, Kundig TM, Merkle HP, Gander B, Johansen P: A protective allergy vaccine based on CpG- and protamine-containing PLGA microparticles. Pharm Res 2007;24:1927–1935.
  12. Barbey C, Donatelli-Dufour N, Batard P, Corradin G, Spertini F: Intranasal treatment with ovalbumin but not the major T cell epitope ovalbumin 323-339 generates interleukin-10 secreting T cells and results in the induction of allergen systemic tolerance. Clin Exp Allergy 2004;34:654–662.
  13. Bohle B, Kinaciyan T, Gerstmayr M, Radakovics A, Jahn-Schmid B, Ebner C: Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation. J Allergy Clin Immunol 2007;120:707–713.
  14. Razafindratsita A, Saint-Lu N, Mascarell L, Berjont N, Bardon T, Betbeder D, Van Overtvelt L, Moingeon P: Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation. J Allergy Clin Immunol 2007;120:278–285.
  15. Zinkernagel RM: Localization dose and time of antigens determine immune reactivity. Semin Immunol 2000;12:163–171; discussion 257–344.
  16. Zinkernagel RM, Ehl S, Aichele P, Oehen S, Kundig T, Hengartner H: Antigen localisation regulates immune responses in a dose- and time-dependent fashion: a geographical view of immune reactivity. Immunol Rev 1997;156:199–209.
  17. Maloy KJ, Erdmann I, Basch V, Sierro S, Kramps TA, Zinkernagel RM, Oehen S, Kundig TM: Intralymphatic immunization enhances DNA vaccination. Proc Natl Acad Sci USA 2001;98:3299–3303.
  18. Johansen P, Haffner AC, Koch F, Zepter K, Erdmann I, Maloy K, Simard JJ, Storni T, Senti G, Bot A, Wuthrich B, Kundig TM: Direct intralymphatic injection of peptide vaccines enhances immunogenicity. Eur J Immunol 2005;35:568–574.
  19. Kundig TM, Bachmann MF, DiPaolo C, Simard JJ, Battegay M, Lother H, Gessner A, Kuhlcke K, Ohashi PS, Hengartner H, et al: Fibroblasts as efficient antigen-presenting cells in lymphoid organs. Science 1995;268:1343–1347.
  20. Crameri R, Fluckiger S, Daigle I, Kundig T, Rhyner C: Design, engineering and in vitro evaluation of MHC class-II targeting allergy vaccines. Allergy 2007;62:197–206.
  21. Arbes SJ Jr, Gergen PJ, Elliott L, Zeldin DC: Prevalences of positive skin test responses to 10 common allergens in the US population: results from the third National Health and Nutrition Examination Survey. J Allergy Clin Immunol 2005;116:377–383.
  22. Beasley R: Worldwide variation in prevalence of sypmtoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 1998;351:1225–1232.
  23. Wuthrich B, Schindler C, Medici TC, Zellweger JP, Leuenberger P: IgE levels, atopy markers and hay fever in relation to age, sex and smoking status in a normal adult Swiss population. SAPALDIA (Swiss Study on Air Pollution and Lung Diseases in Adults) Team. Int Arch Allergy Immunol 1996;111:396–402.
  24. Durham SR, Walker SM, Varga EM, Jacobson MR, O’Brien F, Noble W, Till SJ, Hamid QA, Nouri-Aria KT: Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med 1999;341:468–475.
  25. Bousquet J, Scheinmann P, Guinnepain MT, Perrin-Fayolle M, Sauvaget J, Tonnel AB, Pauli G, Caillaud D, Dubost R, Leynadier F, Vervloet D, Herman D, Galvain S, Andre C: Sublingual-swallow immunotherapy (SLIT) in patients with asthma due to house-dust mites: a double-blind, placebo-controlled study. Allergy 1999;54:249–260.
  26. Nelson HS: Advances in upper airway diseases and allergen immunotherapy. J Allergy Clin Immunol 2005;115:676–684.
  27. Passalacqua G, Guerra L, Pasquali M, Lombardi C, Canonica GW: Efficacy and safety of sublingual immunotherapy. Ann Allergy Asthma Immunol 2004;93:3–12; quiz 12–13, 103.
  28. Canonica GW, Passalacqua G: Noninjection routes for immunotherapy. J Allergy Clin Immunol 2003;111:437–448.
  29. Bousquet J, Van Cauwenberge P, Khaltaev N: Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108:S147–S334.
  30. Koopman G, Bogers WM, van Gils M, Koornstra W, Barnett S, Morein B, Lehner T, Heeney JL: Comparison of intranasal with targeted lymph node immunization using PR8-Flu ISCOM adjuvanted HIV antigens in macaques. J Med Virol 2007;79:474–482.
  31. Trepel M, Arap W, Pasqualini R: Modulation of the immune response by systemic targeting of antigens to lymph nodes. Cancer Res 2001;61:8110–8112.
  32. Lehner T, Wang Y, Ping L, Bergmeier L, Mitchell E, Cranage M, Hall G, Dennis M, Cook N, Doyle C, Jones I: The effect of route of immunization on mucosal immunity and protection. J Infect Dis 1999;179(suppl 3):S489–S492.
  33. Spaner DE, Astsaturov I, Vogel T, Petrella T, Elias I, Burdett-Radoux S, Verma S, Iscoe N, Hamilton P, Berinstein NL: Enhanced viral and tumor immunity with intranodal injection of canary pox viruses expressing the melanoma antigen, gp100. Cancer 2006;106:890–899.
  34. von Beust BR, Johansen P, Smith KA, Bot A, Storni T, Kundig TM: Improving the therapeutic index of CpG oligodeoxynucleotides by intralymphatic administration. Eur J Immunol 2005;35:1869–1876.
  35. Powell RJ, Frew AJ, Corrigan CJ, Durham SR: Effect of grass pollen immunotherapy with Alutard SQ on quality of life in seasonal allergic rhinoconjunctivitis. Allergy 2007;62:1335–1338.
  36. Ruedl C, Bachmann MF, Kopf M: The antigen dose determines T helper subset development by regulation of CD40 ligand. Eur J Immunol 2000;30:2056–2064.
  37. Min B, Paul WE: Basophils: in the spotlight at last. Nat Immunol 2008;9:223–225.
  38. Senti G, Vavricka BM, Erdmann I, Diaz MI, Markus R, McCormack SJ, Simard JJ, Wüthrich B, Crameri R, Graf N, Johansen P, Kündig TM: Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc Natl Acad Sci USA 2008;105:17908–17912.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50