Allergen-specific immunotherapy of allergy and asthma: current and future trends

References

• van Rijt LS, Jung S, Kleinjan A et al.In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma. J. Exp. Med.201(6), 981–991 (2005).
   PubMed Web of Science ®Google Scholar
• Hammad H, Lambrecht BN. Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat. Rev. Immunol.8(3), 193–204 (2008).
   PubMed Web of Science ®Google Scholar
• Walley AJ, Wiltshire S, Ellis CM, Cookson WO. Linkage and allelic association of chromosome 5 cytokine cluster genetic markers with atopy and asthma associated traits. Genomics72(1), 15–20 (2001).
   PubMedGoogle Scholar
• Renauld JC. New insights into the role of cytokines in asthma. J. Clin. Pathol.54(8), 577–589 (2001).
   PubMed Web of Science ®Google Scholar
• Shahana S, Bjornsson E, Ludviksdottir D et al. Ultrastructure of bronchial biopsies from patients with allergic and non-allergic asthma. Respir. Med.99(4), 429–443 (2005).
   PubMed Web of Science ®Google Scholar
• Kay AB. The role of eosinophils in the pathogenesis of asthma. Trends Mol. Med.11(4), 148–152 (2005).
   PubMed Web of Science ®Google Scholar
• Gangur V, Birmingham NP, Thanesvorakul S, Joseph S. CCR3 and CXCR3 as drug targets for allergy: principles and potential. Curr. Drug Targets Inflamm. Allergy2(1), 53–62 (2003).
   PubMedGoogle Scholar
• Truyen E, Coteur L, Dilissen E et al. Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients. Thorax61(3), 202–208 (2006).
   PubMed Web of Science ®Google Scholar
• Barczyk A, Pierzchala W, Sozanska E. Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine. Respir. Med.97(6), 726–733 (2003).
   PubMed Web of Science ®Google Scholar
• Kolls JK, Kanaly ST, Ramsay AJ. Interleukin-17: an emerging role in lung inflammation. Am. J. Respir. Cell. Mol. Biol.28(1), 9–11 (2003).
   PubMed Web of Science ®Google Scholar
• Wang YH, Liu YJ. The IL-17 cytokine family and their role in allergic inflammation. Curr. Opin. Immunol.20(6), 697–702 (2008).
   PubMed Web of Science ®Google Scholar
• Larche M. Regulatory T cells in allergy and asthma. Chest132(3), 1007–1014 (2007).
   PubMed Web of Science ®Google Scholar
• Ling EM, Smith T, Nguyen XD et al. Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet363(9409), 608–615 (2004).
   PubMed Web of Science ®Google Scholar
• Holgate ST, Davies DE, Puddicombe S et al. Mechanisms of airway epithelial damage: epithelial–mesenchymal interactions in the pathogenesis of asthma. Eur. Respir. J.44(Suppl.) S24–S29 (2003).
   Google Scholar
• Kay AB, Phipps S, Robinson DS. A role for eosinophils in airway remodelling in asthma. Trends Immunol.25(9), 477–482 (2004).
   PubMed Web of Science ®Google Scholar
• Bousquet J, Hejjaoui A, Clauzel AM et al. Specific immunotherapy with a standardized Dermatophagoides pteronyssinus extract. II. Prediction of efficacy of immunotherapy. J. Allergy Clin. Immunol.82(6), 971–977 (1988).
   PubMedGoogle Scholar
• Bousquet J, Hejjaoui A, Dhivert H, Clauzel AM, Michel FB. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. Systemic reactions during the rush protocol in patients suffering from asthma. J. Allergy Clin. Immunol.83(4), 797–802 (1989).
   PubMed Web of Science ®Google Scholar
• Holgate ST. Cytokine and anti-cytokine therapy for the treatment of asthma and allergic disease. Cytokine28(4–5), 152–157 (2004).
   PubMed Web of Science ®Google Scholar
• Berry MA, Hargadon B, Shelley M et al. Evidence of a role of tumor necrosis factor a in refractory asthma. N. Engl. J. Med.354(7), 697–708 (2006).
   PubMed Web of Science ®Google Scholar
• Watelet JB, Van Zele T, Gjomarkaj M et al. Tissue remodelling in upper airways: where is the link with lower airway remodelling? Allergy61(11), 1249–1258 (2006).
   PubMed Web of Science ®Google Scholar
• Malling H-J, Weeke B. Position paper: immunotherapy. (EAACI) The European Academy of Allergology and Clinical Immunology. Allergy48(14 Suppl.), 7–35 (1993).
   Google Scholar
• Bousquet J, Michel FB. Specific immunotherapy in asthma: is it effective?. J. Allergy Clin. Immunol.94(1), 1–11 (1994).
   PubMed Web of Science ®Google Scholar
• Bousquet J, Khaltaev N, Cruz AA et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy63(Suppl. 86), 8–160 (2008).
   PubMed Web of Science ®Google Scholar
• Noon L. Prophylactic inoculation for hay fever. Lancet1572–1573 (1911).
   Google Scholar
• van Cauwenberge P, Bachert C, Passalacqua G et al. Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology. Allergy55(2), 116–134 (2000).
   PubMed Web of Science ®Google Scholar
• Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy. J. Allergy Clin. Immunol.119(4), 780–791 (2007).
   PubMed Web of Science ®Google Scholar
• Jutel M, Akdis CA. T-cell regulatory mechanisms in specific immunotherapy. Chem. Immunol. Allergy94, 158–177 (2008).
   PubMedGoogle Scholar
• James LK, Durham SR. Update on mechanisms of allergen injection immunotherapy. Clin. Exp. Allergy38(7), 1074–1088 (2008).
   PubMed Web of Science ®Google Scholar
• Akdis CA, Akdis M, Blesken T et al. Epitope-specific T cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro. J. Clin. Invest.98(7), 1676–1683 (1996).
   PubMed Web of Science ®Google Scholar
• Akdis CA, Blesken T, Akdis M, Wuthrich B, Blaser K. Role of interleukin 10 in specific immunotherapy. J. Clin. Invest.102(1), 98–106 (1998).
   PubMed Web of Science ®Google Scholar
• Akbari O, DeKruyff RH, Umetsu DT. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat. Immunol.2(8), 725–731 (2001).
   PubMed Web of Science ®Google Scholar
• Jutel M, Akdis M, Budak F et al. IL-10 and TGF-β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur. J. Immunol.33(5), 1205–1214 (2003).
   PubMed Web of Science ®Google Scholar
• Jutel M, Pichler WJ, Skrbic D et al. Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-γ secretion in specific allergen-stimulated T cell cultures. J. Immunol.154(8), 4187–4194 (1995).
   PubMed Web of Science ®Google Scholar
• Kämmerer R, Chvatchko Y, Kettner A et al. Modulation of T-cell response to phospholipase A2 and phospholipase A2- derived peptides by conventional bee venom immunotherapy. J. Allergy Clin. Immunol.100(1), 96–103 (1997).
   PubMed Web of Science ®Google Scholar
• Wachholz PA, Nouri-Aria KT, Wilson DR et al. Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1:Th2 cytokine ratios. Immunology, 105(1), 56–62 (2002).
   PubMed Web of Science ®Google Scholar
• Hansen G, Berry G, DeKruyff RH, Umetsu DT. Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation. J. Clin. Invest.103(2), 175–183 (1999).
   PubMed Web of Science ®Google Scholar
• Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY. IgE versus IgG4 production can be differentially regulated by IL-10. J. Immunol.160(7), 3555–3561 (1998).
   PubMed Web of Science ®Google Scholar
• Francis JN, James LK, Paraskevopoulos G et al. Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J. Allergy Clin. Immunol.121(5), 1120–1125 E1122 (2008).
   PubMed Web of Science ®Google Scholar
• Meiler F, Zumkehr J, Klunker S et al.In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure. J. Exp. Med.205(12), 2887–2898 (2008).
   PubMed Web of Science ®Google Scholar
• Wachholz PA, Durham SR. Induction of ‘blocking’ IgG antibodies during immunotherapy. Clin. Exp. Allergy33(9), 1171–1174 (2003).
   PubMed Web of Science ®Google Scholar
• Wachholz PA, Soni NK, Till SJ, Durham SR. Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J. Allergy Clin. Immunol.112(5), 915–922 (2003).
   PubMed Web of Science ®Google Scholar
• Nouri-Aria KT, Wachholz PA, Francis JN et al. Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J. Immunol.172(5), 3252–3259 (2004).
   PubMed Web of Science ®Google Scholar
• Van Ree R, Van Leeuwen WA, Dieges PH et al. Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy. Clin. Exp. Allergy27(1), 68–74 (1997).
   PubMed Web of Science ®Google Scholar
• Francis JN, Till SJ, Durham SR. Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy. J. Allergy Clin. Immunol.111(6), 1255–1261 (2003).
   PubMed Web of Science ®Google Scholar
• Radulovic S, Jacobson MR, Durham SR, Nouri-Aria KT. Grass pollen immunotherapy induces Foxp3-expressing CD4+ CD25+ cells in the nasal mucosa. J. Allergy Clin. Immunol.121(6), 1467–1472 (2008).
   PubMed Web of Science ®Google Scholar
• Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst. Rev.4, CD001186 (2003).
   PubMedGoogle Scholar
• Durham SR, Walker SM, Varga EM et al. Long-term clinical efficacy of grass-pollen immunotherapy. N. Engl. J. Med.341(7), 468–475 (1999).
   PubMed Web of Science ®Google Scholar
• Walker SM, Pajno GB, Lima MT, Wilson DR, Durham SR. Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized, controlled trial. J. Allergy Clin. Immunol.107(1), 87–93 (2001).
   PubMed Web of Science ®Google Scholar
• Pichler CE, Helbling A, Pichler WJ. Three years of specific immunotherapy with house-dust-mite extracts in patients with rhinitis and asthma: significant improvement of allergen-specific parameters and of nonspecific bronchial hyperreactivity. Allergy56(4), 301–306 (2001).
   PubMed Web of Science ®Google Scholar
• Pichler CE, Marquardsen A, Sparholt S et al. Specific immunotherapy with Dermatophagoides pteronyssinus and D. farinae results in decreased bronchial hyperreactivity. Allergy52(3), 274–283 (1997).
   PubMedGoogle Scholar
• Jacobsen L, Nuchel Petersen B, Wihl JA, Lowenstein H, Ipsen H. Immunotherapy with partially purified and standardized tree pollen extracts. IV. Results from long-term (6-year) follow-up. Allergy52(9), 914–920 (1997).
   PubMed Web of Science ®Google Scholar
• Moller C, Dreborg S, Ferdousi HA et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J. Allergy Clin. Immunol.109(2), 251–256 (2002).
   PubMed Web of Science ®Google Scholar
• Jacobsen L, Niggemann B, Dreborg S et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy62(8), 943–948 (2007).
   PubMed Web of Science ®Google Scholar
• Grembiale RD, Camporota L, Naty S et al. Effects of specific immunotherapy in allergic rhinitic individuals with bronchial hyperresponsiveness. Am. J. Respir. Crit. Care Med.162(6), 2048–2052 (2000).
   PubMed Web of Science ®Google Scholar
• Leynaert B, Neukirch C, Kony S et al. Association between asthma and rhinitis according to atopic sensitization in a population-based study. J. Allergy Clin. Immunol.113(1), 86–93 (2004).
   PubMed Web of Science ®Google Scholar
• Shaaban R, Zureik M, Soussan D et al. Rhinitis and onset of asthma: a longitudinal population-based study. Lancet372(9643), 1049–1057 (2008).
   PubMed Web of Science ®Google Scholar
• Des Roches A, Paradis L, Menardo JL et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. J. Allergy Clin. Immunol.99(4), 450–453 (1997).
   PubMed Web of Science ®Google Scholar
• Schadlich PK, Brecht JG. Economic evaluation of specific immunotherapy versus symptomatic treatment of allergic rhinitis in Germany. Pharmacoeconomics17(1), 37–52 (2000).
   PubMed Web of Science ®Google Scholar
• Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J. Allergy Clin. Immunol.102(4 Pt 1), 558–562 (1998).
   PubMed Web of Science ®Google Scholar
• Adkinson NF Jr, Eggleston PA, Eney D et al. A controlled trial of immunotherapy for asthma in allergic children. N. Engl. J. Med.336(5), 324–331 (1997).
   PubMed Web of Science ®Google Scholar
• Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma – Summary Report 2007. J. Allergy Clin. Immunol.120(5 Suppl.), S94–S138 (2007).
   PubMed Web of Science ®Google Scholar
• Winther L, Arnved J, Malling HJ, Nolte H, Mosbech H. Side-effects of allergen-specific immunotherapy: a prospective multi-centre study. Clin. Exp. Allergy36(3), 254–260 (2006).
   PubMed Web of Science ®Google Scholar
• Winther L, Malling HJ, Mosbech H. Allergen-specific immunotherapy in birch- and grass-pollen-allergic rhinitis. II. Side-effects. Allergy55(9), 827–835 (2000).
   PubMed Web of Science ®Google Scholar
• Leynadier F, Banoun L, Dollois B et al. Immunotherapy with a calcium phosphate-adsorbed five-grass-pollen extract in seasonal rhinoconjunctivitis: a double-blind, placebo-controlled study. Clin. Exp. Allergy31(7), 988–996 (2001).
   PubMed Web of Science ®Google Scholar
• Wilson DR, Torres LI, Durham SR. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst. Rev.2, CD002893 (2003).
   Google Scholar
• Bousquet PJ, Demoly P, Passalacqua G, Canonica GW, Bousquet J. Immunotherapy: clinical trials – optimal trial and clinical outcomes. Curr. Opin. Allergy Clin. Immunol.7(6), 561–566 (2007).
   PubMed Web of Science ®Google Scholar
• Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J. Allergy Clin. Immunol.117(4), 802–809 (2006).
   PubMed Web of Science ®Google Scholar
• Pajno GB, Passalacqua G, Vita D et al. Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria-induced respiratory allergy: a randomized controlled trial. Allergy59(8), 883–887 (2004).
   PubMed Web of Science ®Google Scholar
• Di Rienzo V, Marcucci F, Puccinelli P et al. Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study. Clin. Exp. Allergy33(2), 206–210 (2003).
   PubMed Web of Science ®Google Scholar
• Novembre E, Galli E, Landi F et al. Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. J. Allergy Clin. Immunol.114(4), 851–857 (2004).
   PubMed Web of Science ®Google Scholar
• Marogna M, Tomassetti D, Bernasconi A et al. Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study. Ann. Allergy Asthma Immunol.101(2), 206–211 (2008).
   PubMed Web of Science ®Google Scholar
• Andre C, Vatrinet C, Galvain S, Carat F, Sicard H. Safety of sublingual-swallow immunotherapy in children and adults. Int. Arch. Allergy Immunol.121(3), 229–234 (2000).
   PubMed Web of Science ®Google Scholar
• Rodriguez-Perez N, Ambriz-Moreno Mde J, Canonica GW, Penagos M. Frequency of acute systemic reactions in patients with allergic rhinitis and asthma treated with sublingual immunotherapy. Ann. Allergy Asthma Immunol.101(3), 304–310 (2008).
   PubMed Web of Science ®Google Scholar
• Dahl R, Kapp A, Colombo G et al. Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years. J. Allergy Clin. Immunol.121(2), 512–518 e512 (2008).
   PubMed Web of Science ®Google Scholar
• Calamita Z, Saconato H, Pela AB, Atallah AN. Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method. Allergy61(10), 1162–1172 (2006).
   PubMed Web of Science ®Google Scholar
• Dahl R, Kapp A, Colombo G et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J. Allergy Clin. Immunol.118(2), 434–440 (2006).
   PubMed Web of Science ®Google Scholar
• Marogna M, Spadolini I, Massolo A et al. Effects of sublingual immunotherapy for multiple or single allergens in polysensitized patients. Ann. Allergy Asthma Immunol.98(3), 274–280 (2007).
   PubMed Web of Science ®Google Scholar
• Passalacqua G, Musarra A, Pecora S et al. Quantitative assessment of the compliance with once-daily sublingual immunotherapy in children (EASY project: evaluation of a novel SLIT formulation during a year). Pediatr. Allergy Immunol.18(1), 58–62 (2007).
   PubMed Web of Science ®Google Scholar
• Passalacqua G, Durham SR. Allergic rhinitis and its impact on asthma update: allergen immunotherapy. J. Allergy Clin. Immunol.119(4), 881–891 (2007).
   PubMed Web of Science ®Google Scholar
• Jutel M, Jaeger L, Suck R et al. Allergen-specific immunotherapy with recombinant grass pollen allergens. J. Allergy Clin. Immunol.116(3), 608–613 (2005).
   PubMed Web of Science ®Google Scholar
• Pauli G, Larsen TH, Rak S et al. Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis. J. Allergy Clin. Immunol.122(5), 951–960 (2008).
   PubMed Web of Science ®Google Scholar
• Lee TM, Grammer LC, Shaughnessy MA, Patterson R. Modified antigens in the treatment of allergic disease. Year Immunol.2, 338–350 (1986).
   PubMedGoogle Scholar
• Bousquet J, Hejjaoui A, Soussana M, Michel FB. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. IV. Comparison of the safety and efficacy of two dosages of a high-molecular-weight allergoid. J. Allergy Clin. Immunol.85(2), 490–497 (1990).
   PubMed Web of Science ®Google Scholar
• Bousquet J, Maasch HJ, Hejjaoui A et al. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. III. Efficacy and safety of unfractionated and high-molecular-weight preparations in rhinoconjunctivitis and asthma. J. Allergy Clin. Immunol.84(4 Pt 1), 546–556 (1989).
   PubMed Web of Science ®Google Scholar
• Wurtzen PA, Lund L, Lund G et al. Chemical modification of birch allergen extract leads to a reduction in allergenicity as well as immunogenicity. Int. Arch. Allergy Immunol.144(4), 287–295 (2007).
   PubMedGoogle Scholar
• Henmar H, Lund G, Lund L, Petersen A, Wurtzen PA. Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy. Clin. Exp. Immunol.153(3), 316–323 (2008).
   PubMed Web of Science ®Google Scholar
• Ferreira F, Ebner C, Kramer B et al. Modulation of IgE reactivity of allergens by site-directed mutagenesis: potential use of hypoallergenic variants for immunotherapy. FASEB J.12(2), 231–242 (1998).
   PubMed Web of Science ®Google Scholar
• Swoboda I, De Weerd N, Bhalla PL et al. Mutants of the major ryegrass pollen allergen, Lol p 5, with reduced IgE-binding capacity: candidates for grass pollen-specific immunotherapy. Eur. J. Immunol.32(1), 270–280 (2002).
   PubMed Web of Science ®Google Scholar
• Wallner M, Stocklinger A, Thalhamer T et al. Allergy multivaccines created by DNA shuffling of tree pollen allergens. J. Allergy Clin. Immunol.120(2), 374–380 (2007).
   PubMed Web of Science ®Google Scholar
• Kussebi F, Karamloo F, Rhyner C et al. A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy. J. Allergy Clin. Immunol.115(2), 323–329 (2005).
   PubMed Web of Science ®Google Scholar
• Niederberger V, Horak F, Vrtala S et al. Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc. Natl Acad. Sci. USA101(Suppl. 2), 14677–14682 (2004).
   PubMed Web of Science ®Google Scholar
• Pauli G, Purohit A, Oster JP et al. Comparison of genetically engineered hypoallergenic rBet v 1 derivatives with rBet v 1 wild-type by skin prick and intradermal testing: results obtained in a French population. Clin. Exp. Allergy30(8), 1076–1084 (2000).
   PubMed Web of Science ®Google Scholar
• Niederberger V, Reisinger J, Valent P et al. Vaccination with genetically modified birch pollen allergens: immune and clinical effects on oral allergy syndrome. J. Allergy Clin. Immunol.119(4), 1013–1016 (2007).
   PubMed Web of Science ®Google Scholar
• Reisinger J, Horak F, Pauli G et al. Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J. Allergy Clin. Immunol.116(2), 347–354 (2005).
   PubMed Web of Science ®Google Scholar
• Gafvelin G, Thunberg S, Kronqvist M et al. Cytokine and antibody responses in birch-pollen-allergic patients treated with genetically modified derivatives of the major birch pollen allergen Bet v 1. Int. Arch. Allergy Immunol.138(1), 59–66 (2005).
   PubMed Web of Science ®Google Scholar
• Purohit A, Niederberger V, Kronqvist M et al. Clinical effects of immunotherapy with genetically modified recombinant birch pollen Bet v 1 derivatives. Clin. Exp. Allergy38(9), 1514–1525 (2008).
   PubMed Web of Science ®Google Scholar
• Norman PS, Ohman JL Jr, Long AA et al. Treatment of cat allergy with T-cell reactive peptides. Am. J. Respir. Crit. Care Med.154(6 Pt 1), 1623–1628 (1996).
   PubMed Web of Science ®Google Scholar
• Maguire P, Nicodemus C, Robinson D, Aaronson D, Umetsu DT. The safety and efficacy of ALLERVAX CAT in cat allergic patients. Clin. Immunol.93(3), 222–231 (1999).
   PubMed Web of Science ®Google Scholar
• Oldfield WL, Larche 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. Lancet360(9326), 47–53 (2002).
   PubMed Web of Science ®Google Scholar
• Alexander C, Ying S, Kay AB, Larche M. Fel d 1-derived T cell peptide therapy induces recruitment of CD4+ CD25+; CD4+ interferon-γ+ T helper type 1 cells to sites of allergen-induced late-phase skin reactions in cat-allergic subjects. Clin. Exp. Allergy35(1), 52–58 (2005).
   PubMed Web of Science ®Google Scholar
• Oldfield WL, Kay AB, Larche M. 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 (2001).
   PubMed Web of Science ®Google Scholar
• Haselden BM, Larche M, Meng Q et al. Late asthmatic reactions provoked by intradermal injection of T-cell peptide epitopes are not associated with bronchial mucosal infiltration of eosinophils or T(H)2-type cells or with elevated concentrations of histamine or eicosanoids in bronchoalveolar fluid. J. Allergy Clin. Immunol.108(3), 394–401 (2001).
   PubMed Web of Science ®Google Scholar
• Alexander C, Tarzi M, Larche M, Kay AB. The effect of Fel d 1-derived T-cell peptides on upper and lower airway outcome measurements in cat-allergic subjects. Allergy60(10), 1269–1274 (2005).
   PubMed Web of Science ®Google Scholar
• Smith TR, Alexander C, Kay AB, Larche M, Robinson DS. 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. Allergy59(10), 1097–1101 (2004).
   PubMed Web of Science ®Google Scholar
• Verhoef A, Alexander C, Kay AB, Larche M. T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity. PLoS Med.2(3), e78 (2005).
   PubMed Web of Science ®Google Scholar
• Muller U, Akdis CA, Fricker M et al. 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 (1998).
   PubMed Web of Science ®Google Scholar
• Fellrath J-M, Kettner A, Dufour N et al. Allergen specific T cell tolerance induction with allergen-derived long peptides: results of a Phase I safety and immunogenicity trial. J. Allergy Clin. Immunol.111, 854–861 (2003).
   PubMed Web of Science ®Google Scholar
• Corradin G, Spertini F, Verdini A. Medicinal application of long synthetic peptide technology. Expert Opin. Biol. Ther.4(10), 1629–1639 (2004).
   PubMed Web of Science ®Google Scholar
• Audran R, Cachat M, Lurati F et al. Phase I malaria vaccine trial with a long synthetic peptide derived from the merozoite surface protein 3 antigen. Infect. Immun.73(12), 8017–8026 (2005).
   PubMed Web of Science ®Google Scholar
• Sato Y, Roman M, Tighe H et al. Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science273(5273), 352–354 (1996).
   PubMed Web of Science ®Google Scholar
• Spiegelberg HL, Tighe H, Roman M, Broide D, Raz E. Inhibition of IgE formation and allergic inflammation by allergen gene immunization and by CpG motif immunostimulatory oligodeoxynucleotides. Allergy53(45 Suppl.), 93–97 (1998).
   PubMedGoogle Scholar
• Jilek S, Barbey C, Spertini F, Corthesy B. Antigen-independent suppression of the allergic immune response to bee venom phospholipase A(2) by DNA vaccination in CBA/J mice. J. Immunol.166(5), 3612–3621 (2001).
   PubMed Web of Science ®Google Scholar
• Lemieux P. Technological advances to increase immunogenicity of DNA vaccines. Expert Rev. Vaccines1(1), 85–93 (2002).
   PubMedGoogle Scholar
• Santeliz JV, Van Nest G, 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.109(3), 455–462 (2002).
   PubMed Web of Science ®Google Scholar
• Marshall JD, Abtahi S, Eiden JJ et al. Immunostimulatory sequence DNA linked to the Amb a 1 allergen promotes T(H)1 cytokine expression while downregulating T(H)2 cytokine expression in PBMCs from human patients with ragweed allergy. J. Allergy Clin. Immunol.108(2), 191–197 (2001).
   PubMed Web of Science ®Google Scholar
• Tighe H, Takabayashi K, Schwartz D et al. Conjugation of immunostimulatory DNA to the short ragweed allergen Amb a 1 enhances its immunogenicity and reduces its allergenicity. J. Allergy Clin. Immunol.106(1 Pt 1), 124–134 (2000).
   PubMed Web of Science ®Google Scholar
• Tulic MK, Fiset PO, Christodoulopoulos P et al. Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response. J. Allergy Clin. Immunol.113(2), 235–241 (2004).
   PubMed Web of Science ®Google Scholar
• Simons FE, Shikishima Y, Van Nest G, Eiden JJ, HayGlass KT. Selective immune redirection in humans with ragweed allergy by injecting Amb a 1 linked to immunostimulatory DNA. J. Allergy Clin. Immunol.113(6), 1144–1151 (2004).
   PubMed Web of Science ®Google Scholar
• Creticos PS, Schroeder JT, Hamilton RG et al. Immunotherapy with a ragweed-Toll-like receptor 9 agonist vaccine for allergic rhinitis. N. Engl. J. Med.355(14), 1445–1455 (2006).
   PubMed Web of Science ®Google Scholar
• Kline JN. Immunotherapy of asthma using CpG oligodeoxynucleotides. Immunol. Res.39(1–3), 279–286 (2007).
   PubMedGoogle Scholar
• DeFrancesco L. Dynavax trial halted. Nat. Biotechnol.26(5), 484 (2008).
   PubMedGoogle Scholar
• McCormack PL, Wagstaff AJ. Ultra-short-course seasonal allergy vaccine (Pollinex Quattro). Drugs66(7), 931–938 (2006).
   PubMed Web of Science ®Google Scholar
• Baldrick P, Richardson D, Woroniecki SR, Lees B. Pollinex Quattro Ragweed: safety evaluation of a new allergy vaccine adjuvanted with monophosphoryl lipid A (MPL) for the treatment of ragweed pollen allergy. J. Appl. Toxicol.27(4), 399–409 (2007).
   PubMed Web of Science ®Google Scholar
• Drachenberg KJ, Wheeler AW, Stuebner P, Horak F. A well-tolerated grass pollen-specific allergy vaccine containing a novel adjuvant, monophosphoryl lipid A, reduces allergic symptoms after only four preseasonal injections. Allergy56(6), 498–505 (2001).
   PubMed Web of Science ®Google Scholar
• Mothes N, Heinzkill M, Drachenberg KJ et al. Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies. Clin. Exp. Allergy33(9), 1198–1208 (2003).
   PubMed Web of Science ®Google Scholar
• Pearce N, Ait-Khaled N, Beasley R et al. Worldwide trends in the prevalence of asthma symptoms: Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax62(9), 758–766 (2007).
   PubMed Web of Science ®Google Scholar
• Beasley R. The Global Burden of Asthma Report, Global Initiative for Asthma (GINA) (2004).
   Google Scholar
• Seymour SM, Chowdhury BA. Immunotherapy with a ragweed vaccine. N. Engl. J. Med.356(1), 86 (2007).
   PubMedGoogle Scholar
• Larche M. Update on the current status of peptide immunotherapy. J. Allergy Clin. Immunol.119(4), 906–909 (2007).
   PubMed Web of Science ®Google Scholar
• Pauli G, Malling H, Rak S et al. Clinical efficacy of subcutaneous immunotherapy in birch pollen allergic patients: a randomized, double-blind, placebo-controlled study with recombinant Bet v 1 versus natural Bet v 1 or standardized birch extract. Valenta R, Akdis C, Bohle B (Eds). 25th Congress of the European Academy of Allergology and Clinical Immunology. Vienna, Austria, 14–16 June 2006 (Abstract 83).
   Google Scholar
• Pizza M, Giuliani MM, Fontana MR et al. Mucosal vaccines: non toxic derivatives of LT and CT as mucosal adjuvants. Vaccine19(17–19), 2534–2541 (2001).
   PubMed Web of Science ®Google Scholar
• Lambert PH, Laurent PE. Intradermal vaccine delivery: will new delivery systems transform vaccine administration? Vaccine26(26), 3197–3208 (2008).
   PubMed Web of Science ®Google Scholar
• Holland D, Booy R, De Looze F et al. Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: a randomized controlled trial. J. Infect. Dis.198(5), 650–658 (2008).
   PubMed Web of Science ®Google Scholar