Skip to main content
SpringerLink
Log in

T Cell Epitope-Based Allergy Vaccines

  • Chapter
  • First Online:
Vaccines against Allergies

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 352))

Abstract

Specific immunotherapy (SIT) with extracts containing intact allergen molecules is clinically efficacious, but associated with frequent adverse events related to the allergic sensitization of the patient. As a result, treatment is initiated in an incremental dose fashion which ultimately achieves a plateau (maintenance dose) that may be continued for several years. Reduction of allergic adverse events may allow safer and more rapid treatment Thus, many groups have developed and evaluated strategies to reduce allergenicity whilst maintaining immunogenicity, the latter being required to achieve specific modulation of the immune response. Peptide immunotherapy can be used to target T and/or B cells in an antigen-specific manner. To date, only approaches that target T cells have been clinically evaluated. Short, synthetic peptides representing immunodominant T cell epitopes of major allergens are able to modulate allergen-specific T cell responses in the absence of IgE cross linking and activation of effector cells. Here we review clinical and mechanistic studies associated with peptide immunotherapy targeting allergy to cats or to bee venom. 

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alexander C, Ying S, Kay B, Larche M (2005) Fel d 1-derived T cell peptide therapy induces recruitment of CD4CD25; 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(1):52–58

    Article  CAS  PubMed  Google Scholar 

  • Ali FR, Oldfield WL, Higashi N, Larche M, Kay AB (2004) Late asthmatic reactions induced by inhalation of allergen-derived T cell peptides. Am J Respir Crit Care Med 169(1):20–26

    Article  PubMed  Google Scholar 

  • Anderton SM, Burkhart C, Liu GY, Metzler B, Wraith DC (1998) Antigen-specific tolerance induction and the immunotherapy of experimental autoimmune disease. Novartis Found Symp 215:120–131

    CAS  PubMed  Google Scholar 

  • Apostolou I, Von Boehmer H (2004) In vivo instruction of suppressor commitment in naive T cells. J Exp Med 199(10):1401–1408

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bal V, McIndoe A, Denton G, Hudson D, Lombardi G, Lamb J et al (1990) Antigen presentation by keratinocytes induces tolerance in human T cells. Eur J Immunol 20(9):1893–1897

    Article  CAS  PubMed  Google Scholar 

  • Bauer L, Bohle B, Jahn-Schmid B, Wiedermann U, Daser A, Renz H et al (1997) Modulation of the allergic immune response in BALB/c mice by subcutaneous injection of high doses of the dominant T cell epitope from the major birch pollen allergen Bet v 1. Clin Exp Immunol 107(3):536–541

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bockova J, Elias D, Cohen IR (1997) Treatment of NOD diabetes with a novel peptide of the hsp60 molecule induces Th2-type antibodies. J Autoimmun 10(4):323–329

    Article  CAS  PubMed  Google Scholar 

  • Briner TJ, Kuo MC, Keating KM, Rogers BL, Greenstein JL (1993) Peripheral T-cell tolerance induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergen Fel d I. Proc Natl Acad Sci USA 90(16):7608–7612

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Burkhart C, Liu GY, Anderton SM, Metzler B, Wraith DC (1999) Peptide-induced T cell regulation of experimental autoimmune encephalomyelitis: a role for IL-10. Int Immunol 11(10):1625–1634

    Article  CAS  PubMed  Google Scholar 

  • Campbell JD, Buckland KF, McMillan SJ, Kearley J, Oldfield WL, Stern LJ et al (2009) Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression. J Exp Med 206(7):1535–1547

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Carneiro R, Reefer A, Wilson B, Hammer J, Platts-Mills T, Custis N et al (2004) T cell epitope-specific defects in the immune response to cat allergen in patients with atopic dermatitis. J Invest Dermatol 122(4):927–936

    Article  CAS  PubMed  Google Scholar 

  • Chai JG, James E, Dewchand H, Simpson E, Scott D (2004) Transplantation tolerance induced by intranasal administration of HY peptides. Blood 103(10):3951–3959

    Article  CAS  PubMed  Google Scholar 

  • Clayton JP, Gammon GM, Ando DG, Kono DH, Hood L, Sercarz EE (1989) Peptide-specific prevention of experimental allergic encephalomyelitis. Neonatal tolerance induced to the dominant T cell determinant of myelin basic protein J Exp Med 169(5):1681–1691

    Article  CAS  PubMed  Google Scholar 

  • Critchfield JM, Racke MK, Zuniga-Pflucker JC, Cannella B, Raine CS, Goverman J et al (1994) T cell deletion in high antigen dose therapy of autoimmune encephalomyelitis. Science 263(5150):1139–1143

    Article  CAS  PubMed  Google Scholar 

  • Daniel D, Wegmann DR (1996) Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23). Proc Natl Acad Sci USA 93(2):956–960

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Durham SR, Walker SM, Varga EM, Jacobson MR, O’Brien F, Noble W et al (1999) Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med 341(7):468–475

    Article  CAS  PubMed  Google Scholar 

  • Fellrath JM, Kettner A, Dufour N, Frigerio C, Schneeberger D, Leimgruber A et al (2003) Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: results of a phase I trial. J Allergy Clin Immunol 111(4):854–861

    Article  CAS  PubMed  Google Scholar 

  • Gammon G, Dunn K, Shastri N, Oki A, Wilbur S, Sercarz EE (1986) Neonatal T-cell tolerance to minimal immunogenic peptides is caused by clonal inactivation. Nature 319(6052):413–415

    Article  CAS  PubMed  Google Scholar 

  • Gaur A, Wiers B, Liu A, Rothbard J, Fathman CG (1992) Amelioration of autoimmune encephalomyelitis by myelin basic protein synthetic peptide-induced anergy. Science 258(5087):1491–1494

    Article  CAS  PubMed  Google Scholar 

  • Haselden BM, Kay AB, Larche M (1999) Immunoglobulin E-independent major histocompatibility complex-restricted T cell peptide epitope-induced late asthmatic reactions. J Exp Med 189(12):1885–1894

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hoyne GF, O’Hehir RE, Wraith DC, Thomas WR, Lamb JR (1993) 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(5):1783–1788

    Article  CAS  PubMed  Google Scholar 

  • Karin N, Mitchell DJ, Brocke S, Ling N, Steinman L (1994) Reversal of experimental autoimmune encephalomyelitis by a soluble peptide variant of a myelin basic protein epitope: T cell receptor antagonism and reduction of interferon gamma and tumor necrosis factor alpha production. J Exp Med 180(6):2227–2237

    Article  CAS  PubMed  Google Scholar 

  • Kearney ER, Pape KA, Loh DY, Jenkins MK (1994) Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. Immunity 1(4):327–339

    Article  CAS  PubMed  Google Scholar 

  • King TP, Lu G, Agosto H (1998) Antibody responses to bee melittin (Api m 4) and hornet antigen 5 (Dol m 5) in mice treated with the dominant T-cell epitope peptides. J Allergy Clin Immunol 101(3):397–403

    Article  CAS  PubMed  Google Scholar 

  • Kretschmer K, Apostolou I, Hawiger D, Khazaie K, Nussenzweig MC, Von Boehmer H (2005) Inducing and expanding regulatory T cell populations by foreign antigen. Nat Immunol 6:152–162

    Article  Google Scholar 

  • Ku G, Kronenberg M, Peacock DJ, Tempst P, Banquerigo ML, Braun BS et al (1993) Prevention of experimental autoimmune arthritis with a peptide fragment of type II collagen. Eur J Immunol 23(3):591–599

    Article  CAS  PubMed  Google Scholar 

  • Lamb JR, Skidmore BJ, Green N, Chiller JM, Feldmann M (1983) Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin. J Exp Med 157(5):1434–1447

    Article  CAS  PubMed  Google Scholar 

  • Maguire P, Nicodemus C, Robinson D, Aaronson D, Umetsu DT (1999) The safety and efficacy of ALLERVAX CAT in cat allergic patients. Clin Immunol 93(3):222–231

    Article  CAS  PubMed  Google Scholar 

  • Marcotte GV, Braun CM, Norman PS, Nicodemus CF, Kagey-Sobotka A, Lichtenstein LM et al (1998) Effects of peptide therapy on ex vivo T-cell responses. J Allergy Clin Immunol 101(4 Pt 1):506–513

    Article  CAS  PubMed  Google Scholar 

  • Metzler B, Wraith DC (1993) Inhibition of experimental autoimmune encephalomyelitis by inhalation but not oral administration of the encephalitogenic peptide: influence of MHC binding affinity. Int Immunol 5(9):1159–1165

    Article  CAS  PubMed  Google Scholar 

  • Muller U, Akdis CA, Fricker M, Akdis M, Blesken T, Bettens F et al (1998) Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. J Allergy Clin Immunol 101(6 Pt 1):747–754

    Article  CAS  PubMed  Google Scholar 

  • Norman PS, Ohman JL, Long AA, Creticos PS, Gefter MA, Shaked Z et al (1996) Treatment of cat allergy with T-cell reactive peptides. Am J Respir Crit Care Med 154(6 Pt 1):1623–1628

    Article  CAS  PubMed  Google Scholar 

  • Novak N, Bieber T, Katoh N (2001) Engagement of Fc epsilon RI on human monocytes induces the production of IL-10 and prevents their differentiation in dendritic cells. J Immunol 167(2):797–804

    CAS  PubMed  Google Scholar 

  • Oldfield WL, Kay AB, Larche M (2001) Allergen-derived T cell peptide-induced late asthmatic reactions precede the induction of antigen-specific hyporesponsiveness in atopic allergic asthmatic subjects. J Immunol 167(3):1734–1739

    CAS  PubMed  Google Scholar 

  • Oldfield WL, Larche M, Kay AB (2002) Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial. Lancet 360(9326):47–53

    Article  CAS  PubMed  Google Scholar 

  • Pene J, Desroches A, Paradis L, Lebel B, Farce M, Nicodemus CF et al (1998) Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats. J Allergy Clin Immunol 102(4 Pt 1):571–578

    Article  CAS  PubMed  Google Scholar 

  • Prakken BJ, van Der ZR, Anderton SM, van Kooten PJ, Kuis W, van Eden W (1997) Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis. Proc Natl Acad Sci USA 94(7):3284–3289

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Reefer AJ, Carneiro RM, Custis NJ, Platts-Mills TA, Sung SS, Hammer J et al (2004) A role for IL-10-mediated HLA-DR7-restricted T cell-dependent events in development of the modified Th2 response to cat allergen. J Immunol 172(5):2763–2772

    CAS  PubMed  Google Scholar 

  • Santambrogio L, Sato AK, Fischer FR, Dorf ME, Stern LJ (1999a) Abundant empty class II MHC molecules on the surface of immature dendritic cells. Proc Natl Acad Sci USA 96(26):15050–15055

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Santambrogio L, Sato AK, Carven GJ, Belyanskaya SL, Strominger JL, Stern LJ (1999b) Extracellular antigen processing and presentation by immature dendritic cells. Proc Natl Acad Sci USA 96(26):15056–15061

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Simons FE, Imada M, Li Y, Watson WT, HayGlass KT (1996) Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects. Int Immunol 8(12):1937–1945

    Article  CAS  PubMed  Google Scholar 

  • Smith TR, Alexander C, Kay AB, Larche M, Robinson DS (2004) Cat allergen peptide immunotherapy reduces CD4 T cell responses to cat allergen but does not alter suppression by CD4 CD25 T cells: a double-blind placebo-controlled study. Allergy 59(10):1097–1101

    Article  CAS  PubMed  Google Scholar 

  • Staines NA, Harper N, Ward FJ, Malmstrom V, Holmdahl R, Bansal S (1996) Mucosal tolerance and suppression of collagen-induced arthritis (CIA) induced by nasal inhalation of synthetic peptide 184-198 of bovine type II collagen (CII) expressing a dominant T cell epitope. Clin Exp Immunol 103(3):368–375

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Steinman RM, Hawiger D, Nussenzweig MC (2003) Tolerogenic dendritic cells. Annu Rev Immunol 21:685–711.

    Article  CAS  PubMed  Google Scholar 

  • Tarzi M, Klunker S, Texier C, Verhoef A, Stapel SO, Akdis C et al (2005) Induction of interleukin-10 and suppressor of cytokine signaling-3 gene expression following peptide immunotherapy. Clin Exp Allergy

    Google Scholar 

  • Texier C, Pouvelle S, Busson M, Herve M, Charron D, Menez A et al (2000) HLA-DR restricted peptide candidates for bee venom immunotherapy. J Immunol 164(6):3177–3184

    CAS  PubMed  Google Scholar 

  • Tian J, Atkinson MA, Clare-Salzler M, Herschenfeld A, Forsthuber T, Lehmann PV et al (1996) Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. J Exp Med 183(4):1561–1567

    Article  CAS  PubMed  Google Scholar 

  • Verhoef A, Alexander C, Kay AB, Larche M (2005) T cell epitope immunotherapy induces a CD4(+) T cell population with regulatory activity. PLoS Med 2(3):e78

    Article  PubMed Central  PubMed  Google Scholar 

  • von Garnier C, Astori M, Kettner A, Dufour N, Heusser C, Corradin G et al (2000) Allergen-derived long peptide immunotherapy down-regulates specific IgE response and protects from anaphylaxis. Eur J Immunol 30(6):1638–1645

    Article  Google Scholar 

  • Wraith DC, Goldman M, Lambert PH (2003) Vaccination and autoimmune disease: what is the evidence? Lancet 362(9396):1659–1666

    Article  CAS  PubMed  Google Scholar 

  • Wraith DC, Nicolson KS, Whitley NT (2004) Regulatory CD4(+) T cells and the control of autoimmune disease. Curr Opin Immunol 16(6):695–701

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author is funded by the Canada Research Chairs program, a McMaster University/GlaxoSmithKline Chair in Lung Immunology at St. Joseph's Healthcare, the Canadian Institutes for Health Research, AllerGen Network of Centres of Excellence and the Canadian Foundation for Innovation.

Author information

Authors and Affiliations

  1. Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, HSC 4H20, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada

    Mark Larché

Authors
  1. Mark Larché
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Larché .

Editor information

Editors and Affiliations

  1. Christian Doppler Laboratory for Allergy, Medical University of Vienna, Vienna, Austria

    Rudolf Valenta

  2. Dynavax Technologies, Berkeley, California, USA

    Robert L. Coffman

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Larché, M. (2011). T Cell Epitope-Based Allergy Vaccines. In: Valenta, R., Coffman, R. (eds) Vaccines against Allergies. Current Topics in Microbiology and Immunology, vol 352. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2011_131

Download citation

Publish with us

Policies and ethics

Search

Navigation