Skip to main content
SpringerLink
Log in

The Roots and Growth of Allergen Immunotherapy

  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Abstract

Purpose of Review

The purpose of this review is to present the history of allergen immunotherapy.

Recent Findings

An overview of allergen immunotherapy suggests its roots comes from the immunological treatment of contagious disease. The idea, beginning in the 18th century, that one could be protected against certain illnesses was extended to the field of allergy successfully in 1911.

Summary

This review presents highlights of the advances by many of the individuals who have contributed to the science of allergen immunotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Humphrey JH, White RG. Immunology for students of medicine. Oxford: Blackwell Scientific Publications; 1970;Chapter 1. p. 1.

    Google Scholar 

  2. Cooke RA. Section 1. Fundamental aspects of allergy. Philadelphia: WB Saunders Company; 1947. p. 1.

    Google Scholar 

  3. Jenner E. An inquiry into the causes and effects of the variolae… Sampson Low. London: Soho; 1798.

    Google Scholar 

  4. Blackley CH. Experimental researches on the causes and nature of catarrhus aestivus. London: Bailliere, Tindall and Cox; 1873.

    Google Scholar 

  5. Noon L. Prophylactic inoculation against hay fever. Lancet. 1911;1:1572.

    Article  Google Scholar 

  6. Blakely CH. Hay Fever; its causes, treatment, and effective prevention. London: Balliere; 1880.

    Google Scholar 

  7. Dunbar WP. The present state of our knowledge of hay-fever. J Hygiene. 1902;13:105.

    Article  Google Scholar 

  8. Freeman J. Vaccination against hay fever. Report of Results During The Last Three Years. Lancet. 1914;1:1178.

    Article  Google Scholar 

  9. Rackemann FM. Robert Anderson Cooke. 1880-1960. Trans Assoc Am Physicians. 1961;74:11–3.

    CAS  PubMed  Google Scholar 

  10. •• Cooke RA, Vander VA. Human sensitization. J Immunol. 1916;1:201–305. Iconic lengthy summary of what was known by 1916.

  11. Schloss OM. A case of allergy to common foods. Am J Dis Child. 1912;111:341.

    Google Scholar 

  12. Wodehouse RP. Immunochemical study and immunochemistry of protein series. J Immunol. 1917; 11:227, 237, 243

  13. Walker IC. Studies on the sensitization of patients with bronchial asthma. J Med Res. 1917:35–7.

  14. Cooke RA. Studies in specific hypersensitiveness. III. On constitutional reactions: the dangers of the diagnostic cutaneous test and therapeutic injection of allergens. J Immunol. 1922;7:119–46.

    Article  CAS  Google Scholar 

  15. Coca AF. Studies in specific hypersensitiveness. V. The preparation of fluid extracts and solutions for use in the diagnosis and treatment of the allergies with notes on the collection of pollen. J Immunol. 1922;7:163–78.

    Article  CAS  Google Scholar 

  16. Cooke RA. Studies in specific hypersensitiveness. IX. On the phenomenon of hyposensitization (The clinically lessened sensitiveness of allergy). J Immuniol. 1922;7:219–42.

    Article  CAS  Google Scholar 

  17. •• Prausnitz Cand Kustner H. Studien uber Uberempfindlichkeit. CentralblfBacteriol, 1AbtOrig. 1921;86:160–9. Classid paper on Allergy transfer.

  18. Cohen SG, Zelaya-Quesada M. Prausnitz and Küstner phenomenon: the P-K reaction. J Allergy Clin Immunol. 2004;118:705–10.

    Article  Google Scholar 

  19. Vander Veer A, Cooke RA, Spain WC. Diagnosis and treatment of seasonal hay fever. Am J Med Sci. 1927;174:101.

    Article  Google Scholar 

  20. Frankland AW, Hughes WH, Garrill RH. Autogenous bacterial vaccines in the treatment of asthma. Br Med J. 1955;2:941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Helander E. Bacterial vaccines in the treatment of bronchial asthma. Acta Allergol. 1959;13:47.

    Article  Google Scholar 

  22. Johnstone DE. Study of the value of bacterial vaccines in the treatment of bronchial asthma associated with respiratory infections. AMA J Dis Child. 1957;94:1.

    CAS  PubMed  Google Scholar 

  23. •• Lichtenstein LM, Valentine MD, Sobotka AK. A case for venom treatment in anaphylactic sensitivity to Hymenoptera sting. N Engl J Med. 1974;290:1223–7. Paper that changed treatment of hymenoptera hypersensivity.

  24. Wauter RH, Brooks DI, Schwartz DJ. Imported fire ant immunotherapy prescribing patterns in a large health care system during an 11-year period. Ann Allergy Asthma Immunol. 2020;125:577–80.

    Article  Google Scholar 

  25. Cohen S. Loveless on wasp venom allergy and immunity. Parts 1,2. The allergy archives. J Allergy Clin Immunol. 2003;112:1248–54.

    Article  PubMed  Google Scholar 

  26. • Loveless MH, Feckler WR. Wasp venom allergy and immunity. Ann Alllergy. 1956;14:347–66. Report of this unsung heroine's work on insect sting anaphylaxis.

  27. Cooke RA. Allergy in theory and practice. Philadelphia and London: WB Saunders Company; 1947. p. 203.

    Google Scholar 

  28. Nelson HS. Long-term immunotherapy with aqueous and alum precipitated grass extracts. Ann Allergy. 1980;45:333.

    CAS  PubMed  Google Scholar 

  29. Potter M, Boyce CR. Induction of plasma cell neoplasms in strains BALB/c mice with mineral oil and mineral oil adjuvants. Nature. 1962;193:1086.

    Article  CAS  PubMed  Google Scholar 

  30. Valenta R, Duchene M, Birkner VS, et al. Look up. J Clin Invest. 1997;99:1673.

    PubMed  PubMed Central  Google Scholar 

  31. Focke-tejkl M, Weber M, Niespodziana K, Neubauer A, et al. Development and characterization of a recombinant, hypoallergenic, peptide-based vaccine for grass pollen allergy. J Allergy Clin Immunol. 2015;135:1207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. •• Ishizaka K, Ishizaka T. Identification of ϒ E-antibodies as a carrier of reaginic activity. J Immunol. 1967;99:1187–98. Co-Seminal paper on discovery IgE.

  33. •• Johannson SG. Raised levels of a new immunoglobulin class (IgND) in asthma. Lancet. 1967;ii:951–3. Co-Seminal Paper on discovery of IgE.

  34. Sherman WB. Reaginic and blocking antibodies. J Allergy. 1957;28:62.

    Article  CAS  PubMed  Google Scholar 

  35. Ishizaka K, Ishizaka T. Identification of ϒ E-antibodies as a carrier of reaginic activity. J Immunol. 1967;99:1187–98.

    Article  CAS  PubMed  Google Scholar 

  36. Johannson SG. Raised levels of a new immunoglobulin class (IgND) in asthma. Lancet. 1967;ii:951–9.

    Article  Google Scholar 

  37. Cook RA, Barnard JH, Stull HS. Serological evidence of immunity with coexisting sensation in a type of human allergy. (hay fever). J Exp Med. 1935;62:733.

    Article  Google Scholar 

  38. Durham S, Leung DY. One hundred years of allergen immunotherapy. Time to ring in the changes. JAllergy Clin Immunol. 2011;127:3–7.

    Article  Google Scholar 

  39. Noon L. Prophylactic inoculation against hay fever. Lancet. 1911;1:1572.

    Article  Google Scholar 

  40. Prausnitz C, Küstner H. Studien über die Ueberempfindlichkeit. Zentralbl Bakteriol. 1921;86:160–9.

    CAS  Google Scholar 

  41. Freeman J. Rush inoculation with special reference to hay fever treatment. Lancet. 1930;1:744.

    Article  Google Scholar 

  42. Cooke RA, Barnard JH, Hebald S, Stull A. Serological immunity with co-existing sensitisation in a type of human allergy (hay fever). J Exp Med. 1935;62:733–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. • Frankland AW, Augustin R. Prophylaxis of summer hay fever and asthma: controlled trial comparing crude grass pollen extracts with isolated main protein. Lancet. 1954;266(2821):1055–7. First double-blind, placebo-controlled, subcutaneous grass pollen immunotherapy trial.

  44. Lowell FC, Franklin W. A double-blind study of the effectiveness and specificity of injection therapy in ragweed hay fever. N Engl J Med. 1965;273:675–9.

    Article  CAS  PubMed  Google Scholar 

  45. Ishizaka K, Ishizaka T, Hornbrook MM. Physicochemical properties of reaginic antibody V. Correlation of reaginic activity with IgE globulin antibody. J Immunol. 1966;97:840–53

  46. Johansson SGO, Bennich H. Studies on a new class of human immunoglobulins. 1.Immunological properties. Nobel symposium 3,gamma globulins, structure and control of biosynthesis. Stockholm: Almqvist and Wiksell; 1967. p. 193.

    Google Scholar 

  47. Hunt KJ, Valentine MD, Sobotka AK, Benton AW, Amodio FJ, Lichtenstein LM. A controlled trial of immunotherapy in insect hypersensitivity. N Engl J Med. 1978;299:157–61.

    Article  CAS  PubMed  Google Scholar 

  48. Johnstone DE, Dutton A. The value of hyposensitization therapy for bronchial asthma in children-a 14-year study. Pediatrics. 1968;42:793–802.

    Article  CAS  PubMed  Google Scholar 

  49. Warner JO, Price JF, Soothill JF, Hey EN. Controlled trial of hyposensitisation to Dermatophagoides pteronyssinus in children with asthma. Lancet. 1978;2:912–5.

    Article  CAS  PubMed  Google Scholar 

  50. Rocklin RE, Sheffer AL, Greineder DK, Melmon KL. Generation of antigen specific suppressor cells during allergy desensitization. N Engl J Med. 1980;302:1213–9.

    Article  CAS  PubMed  Google Scholar 

  51. Gleich GJ, Zimmermann EM, Henderson LL, Yunginger JW. Effect of immunotherapy on immunoglobulin E and immunoglobulin G antibodies to ragweed antigens: a six-year prospective study. J Allergy Clin Immunol. 1982;70:261–71.

    Article  CAS  PubMed  Google Scholar 

  52. Scadding GK, Brostoff J. Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite. Clin Allergy. 1986;16:483–91.

    Article  CAS  PubMed  Google Scholar 

  53. • Creticos PS, Marsh DG, Proud D, Kagey-Sobotka A, Adkinson NF Jr, Friedhoff L, et al. Responses to ragweed-pollen nasal challenge before and after immunotherapy. J Allergy Clin Immunol. 1989;84:197–205. An important Dose-Efficay study for Ragweed hypersensitivity.

  54. Rak S, Björnson A, Hakanson L, Sörenson S, Venge P. The effect of immunotherapy on eosinophil accumulation and production of eosinophil chemotactic activity in the lung of subjects with asthma during natural pollen exposure. J Allergy Clin Immunol. 1991;88:878–88.

    Article  CAS  PubMed  Google Scholar 

  55. Norman PS, Ohman JL Jr, Long AA, Creticos PS, Gefter MA, Shaked Z, et al. Treatment of cat allergy with T cell reactive peptides. Am J Respir Crit Care. 1996;154:1623–8.

    Article  CAS  Google Scholar 

  56. Akdis CA, Blesken T, Akdis M, Wüthrich B, Blaser K. Role of interleukin 10 in specific immunotherapy. J Clin Invest. 1998;1021:98–106.

    Article  Google Scholar 

  57. Passalacqua G, Albano M, Fregonese L, Riccio A, Pronzato C, Mela GS, et al. Randomized controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis. Lancet. 1998;351:629–32.

    Article  CAS  PubMed  Google Scholar 

  58. Durham SR, Walker SM, Varga EM, Jacobson MR, O’Brien F, Noble W, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999;341:468–75.

    Article  CAS  PubMed  Google Scholar 

  59. Niederberger V, Horak F, Vrtala S, Spitzauer S, Krauth MT, Valent P, et al. Vaccination with genetically engineered allergens prevents progression of allergic. Proc Natl Acad Sci U S A. 2004;101:14677–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Creticos PS, Schroeder JT, Hamilton RG, Balcer-Whaley SL, Khattignavong AP, Lindblad R, et al. Immunotherapy with a ragweed-toll-like receptor 9 agonist. N Engl J Med. 2006;355:1445–55.

  61. Jacobsen L, Niggemann B, Dreborg S, Ferdousi HA, Halken S, Høst A, et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial. Allergy. 2007;62:943–8.

    Article  CAS  PubMed  Google Scholar 

  62. Durham SR, Emminger W, Kapp A, Colombo G, de Monchy JG, Rak S, et al. Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. J Allergy Clin Immunol. 2010;125:131–8.

    Article  CAS  PubMed  Google Scholar 

  63. Lowell FC, Franklin W. A double blind study of the effectiveness and specificity of injection therapy in ragweed hay fever. New Engl J Med. 1965;273:675.

    Article  CAS  PubMed  Google Scholar 

  64. Fontana VC, Holt LE Jr, Mainland D. Effectiveness of hyposensitization therapy in ragweed hay-fever in children. JAMA. 1967;195:109.

    Google Scholar 

  65. Norman PS, Winkenwerder WL, Lichtenstein LM. Immunotherapy of hay fever with ragweed antigen E: comparisons with whole pollen extracts and placebos. J Allergy. 1968;42:93.

    Article  CAS  PubMed  Google Scholar 

  66. Abramson MJ, Puy RM, Weiner JM. Injection allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2010;(8):CD001186. https://doi.org/10.1002/14651858.CD.

  67. Ross RN, Nelson HS, Finegold I. Effectiveness of specific immunotherapy in the treatment of asthma: a meta-analysis of prospective, randomized, double-blind, placebo-controlled studies. Clin Ther. 2000;22:329–41.

    Article  CAS  PubMed  Google Scholar 

  68. Report of the Joint Committee on Standards 1935 J Allergy. 6:408.

  69. Joint Task Force. Practice parameters for allergen immunotherapy. JACI. 1996;98:1001–11.

    Google Scholar 

  70. Johnstone DE, Dutton A. The value of hyposensitization therapy for bronchial asthma in children – a 14-year study. Pediatrics. 1968;42:793–802.

    Article  CAS  PubMed  Google Scholar 

  71. Durham SR, Walker SM, Varga EM, Jacobson MR, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999;341:468–75.

    Article  CAS  PubMed  Google Scholar 

  72. Schoffield AT. A case of egg poisoning. Lancet. 1908;1:716.

    Article  Google Scholar 

  73. Canonica GW, Bousquet J, Casale T, Lockey RF, et al. Sub-lingual immunotherapy: world allergy position paper 2009. World Allergy Org J. 2009;2:233.

    Article  Google Scholar 

  74. Cohen SG. Evans RE. Allergen immunotherapy in historical perspective. In Lockey and Bukantz Ed.: Allergens and Immunotherapy. Marcel Decker, Inc. NY 1999. 1–37

  75. Cohen, SG, Samter M. Excerpts from Classics in Allergy. Second ed. Symposia Foundation, Carlsbad, CA. 1992

  76. Finegold I, Dockhorn R, Ein D, et al. Immunotherapy throughout the decades: from Noon to now. Ann Allergy Asthma Immunol. 2010;105(5):328–36.

    Article  CAS  PubMed  Google Scholar 

  77. Nelson H. The evolution of allergy immunotherapy. Ann Allergy Asthma Immunol. 2021;126:357–66.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Allergy and Immunology Mount Sinai West and Morningside, Cooke Institute of Allergy, Icahn School of Medicine at Mount Sinai, 121 East 60th Street Suite 4C, New York, NY, 10022, USA

    Ira Finegold MD, MS, FACAAI, FAAAAI, FACP

Authors
  1. Ira Finegold MD, MS, FACAAI, FAAAAI, FACP
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ira Finegold MD, MS, FACAAI, FAAAAI, FACP.

Ethics declarations

Conflict of Interest

The author declares that no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Finegold, I. The Roots and Growth of Allergen Immunotherapy. Curr Treat Options Allergy 10, 340–349 (2023). https://doi.org/10.1007/s40521-023-00348-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40521-023-00348-3

Keywords

Search

Navigation