Concepts and perspectives on peptide-based immunotherapy in allergy

Briner TJ, Kuo MC, Keating KM, Rogers BL, Greenstein JL. 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 1993; 90:7608–12

Hoyne GF, O’Hehir RE, Wraith DC, Thomas WR, Lamb J. R. 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 1993;178:1783–8

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 I Respir Crit Care Med 1996;154:1623–8

Haselden BM, Kay AB, Larché M. Immunoglobulin E-independent major histocompatibility complex-restricted T cell peptide epitope-induced late asthmatic reactions. J Exp Med. 1999 Jun 21;189:1885–94

Simons FE, Imada M, Li Y, Watson WT, HayGlass KT. Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects. Int Immunol 1996; 8:1937–45

Pène J, Desroches A, Paradis L, Lebel B, Farce M, Nicodemus CF, et al. Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats. J Allergy Clin Immunol 1998;102:571–8

Maguire P, Nicodemus C, Robinson D, Aaronson D, Umetsu DT. The safety and efficacy of ALLERVAX CAT in cat allergic patients. Clin Immunol 1999;93:222–31

Creticos PS, Hebert J, Philip G and the Allervax® Ragweed Study Group. Efficacy of Allervax® ragweed in the treatment of ragweed-induced allergy. J Allergy Clin Immunol 1997;99:S401

Muller U, Akdis C, Fricker M, Akdis M, Blesken T, Bettens F, et al. Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A, induces specific T-cell anergy in patients allergic to bee venom. J Allergy Clin lmmunol 1998;101:747–54

Tarzi M, Klunker S, Texier C, Verhoef A, Stapel SO, Akdis CA, et al. Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy. Clin Exp Allergy. 2006;36:465–74

Oldfield WL, Kay AB, Larché M. Allergen-derived T cell peptide-induced late asthmatic reactions precede the induction of antigen-specific hyporesponsiveness in atopic allergic asthmatic subjects. J Immunol 2001;167:1734–9

Oldfield WL, Larché M, Kay AB. 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 2002;360:47–53

Alexander C, Tarzi M, Larché M, Kay AB. The effect of Fel d 1-derived T-cell peptides on upper and lower airway outcome measurements in cat-allergic subjects. Allergy. 2005 Oct;60:1269–74

Niederberger V, Horak F, Vrtala S, Spitzauer S, Krauth MT, Valent P, et al. Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc Natl Acad Sci U S A. 2004;101 Suppl 2:14677–82

Fellrath JM, Kettner A, Dufour N, Frigerio C, Schneeberger D, Leimgruber A, et al. Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: results of a phase I trial. J Allergy Clin Immunol 2003;111:854–61

Spertini F, Perrin Y, Audran R, Pellaton C, Boudousquié C, Barbier N, et al. Safety and immunogenicity of immunotherapy with Bet v 1-derived contiguous overlapping peptides. J Allergy Clin Immunol. 2014;134:239–240.e13

Worm M, Lee HH, Kleine-Tebbe J, Hafner RP, Laidler P, Healey D, et al. Development and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy. J Allergy Clin Immunol 2011;127:89–97, 97.e1–14

Worm M, Patel D, Creticos PS. Cat peptide antigen desensitisation for treating cat allergic rhinoconjunctivitis. Expert Opin Investig Drugs 2013;22:1347–57

Patel D, Couroux P, Hickey P, Salapatek AM, Laidler P, Larche M, et al. Fel d 1—derived peptide antigen desensitization shows a persistent treatment effect 1 year after the start of dosing: A randomized, placebo-controlled study. Journal of Allergy and Clinical Immunology 2013;131:103–7

Couroux P, Patel D, Armstrong K, Larche M, Hafner R. Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term treatment effect in cat allergic subjects. Clin Exp Allergy 2015;45:974–81

Larche M, Hickey P, Hebert J, Hafner R. Safety and Tolerability of Escalating Doses of House Dust Mite- Peptide Antigen Desensitization (HDM-PAD) J Allergy Clin Immunol 2013;131:Supplement:AB37–135

Hafner R, Couroux P, Armstrong K, Salapatek AM, Patel D, Larche M, et al. Persistent treatment effect achieved at one year after four doses of Der p derived synthetic peptide immuno-regulatory epitopes in an exposure chamber model of House Dust Mite allergy. J Allergy Clin Immunol 2014;133:AB289–998

Hafner RP, Salapatek AM, Larché M, Ahenkorah B, Patel P, Pawsey S. Comparison of the treatment effect of house dust mite synthetic peptides immune-regulatory epitopes in the environmental exposure chamber and field setting two years after a short course of treatment. Allergy 2015; 70 Supplement: 28

Pawsey S, Patel D, Hafner R, Hickey P, Powell J. Safety of House Dust Mite synthetic peptide immuno-regulatory epitopes in patients with House Dust Mite allergy and controlled asthma. J Allergy Clin Immunol 2015;135:AB142–461

Ellis AK, Frankish CW, O’Hehir RE, Armstrong K, Steacy L, Larché M et al. Treatment with grass allergen peptides improves symptoms of grass pollen induced allergic rhinoconjunctivitis. J Allergy Clin Immunol 2016 (submitted)

Hafner R, Salapatek AM, Patel D, Larche M, Laidler P. Validation of peptide immunotherapy as a new approach in the treatment of allergic rhinoconjunctivitis: the clinical benefits of treatment with Amb a 1 derived T cell epitopes. J Allergy Clin Immunol 2012;129:AB368–L16

Larché M, Akdis CA, Valenta R. Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol. 2006;6:761–71

Francis JN, Till SJ, Durham SR. Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy. J Allergy Clin Immunol. 2003;111:1255–61

Francis JN, James LK, Paraskevopoulos G, Wong C, Calderon MA, Durham SR, et al. Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J Allergy Clin Immunol. 2008;121:1120–1125.e2

Akdis CA, Blesken T, Akdis M, Wüthrich B, Blaser K. Role of interleukin 10 in specific immunotherapy. J Clin Invest 1998;102:98–106

Secrist H, Chelen CJ, Wen Y, Marshall JD, Umetsu DT. Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals. J Exp Med. 1993;178:2123–30

Varney VA, Hamid QA, Gaga M, Ying S, Jacobson M, Frew AJ, et al. Influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. J Clin Invest. 1993;92:644–51

Campbell JD, Buckland KF, McMillan SJ, Kearley J, Oldfield WL, et al. Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression. J Exp Med 2009;206:1535–47

Verhoef A, Alexander C, Kay AB, Larché M. T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity. PLoS Med 2005;2:e78

Alexander C, Ying S, B Kay A, Larché 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 2005;35:52–8

Moldaver DM, Bharhani MS, Wattie JN, Ellis R, Neighbour H, Lloyd CM, et al. Amelioration of ovalbumin-induced allergic airway disease following Der p 1 peptide immunotherapy is not associated with induction of IL-35. Mucosal Immunol 2014;7:379–90