Akinbami LJ, Moorman JE, Bailey C. Trends in asthma prevalence, health care use, and mortality in the United States, 2001–2010. NCHS data brief, no 94. Hyattsville: National Center for Health Statistics; 2012.Google Scholar
Barnett SB, Nurmagambetov TA. Costs of asthma in the United States: 2002-2007. J Allergy Clin Immunol. 2011;127:145–52.PubMedCrossRefGoogle Scholar
Wallace D, Dykewicz M, Bernstein D, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allerg Clin Immunol. 2008;122:S1–S84.CrossRefGoogle Scholar
Soni A allergic rhinitis: trends in use and expenditures, 2000 and 2005. Medical Expenditure Panel Survey. Statistical Brief #204: May 2008. http://www.meps.ahrq.gov/mepsweb/data_files/publications/st204/stat204.pdf
Schoenwetter WF, Dupclay Jr L, Appajosyula S, Botteman MF, Pashos CL. Economic impact and quality-of-life burden of allergic rhinitis. Curr Med Res Opin. 2004;20:305–17.PubMedCrossRefGoogle Scholar
• Durham SR, Emminger W, Kapp A, et al. SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J Allergy Clin Immunol. 2012;129:717–25 e5. Study demonstrating the persistent efficacy of SLIT after treament discontinuation
Marogna M, Spadolini I, Massolo A, Canonica GW, Passalacqua G. Long-lasting effects of sublingual immunotherapy according to its duration: a 15-year prospective study. J Allergy Clin Immunol. 2010;126:969–75.PubMedCrossRefGoogle Scholar
Hankin CS, Cox L, Wang Z, Bronstone A. Does Allergen-specific immunotherapy provide cost benefits for children and adults with allergic rhinitis? Results from large-scale retrospective analyses jointly funded by AAAAI and ACAAI. J Allerg Clin Immunol. 2011;127:AB73.CrossRefGoogle Scholar
• Lockey RF, Hankin CS. Health economics of allergen-specific immunotherapy in the United States. J Allergy Clin Immunol. 2011;127:39–43. Brief but fairly complete review of the cost-efficacy of AIT
Strunk RC, Sternberg AL, Szefler SJ, Zeiger RS, Bender B, Tonascia J. Long-term budesonide or nedocromil treatment, once discontinued, does not alter the course of mild to moderate asthma in children and adolescents. J Pediatr. 2009;154:682–7.PubMedCrossRefGoogle Scholar
Ariano R, Berto P, Tracci D, Incorvaia C, Frati F. Pharmacoeconomics of allergen immunotherapy compared with symptomatic drug treatment in patients with allergic rhinitis and asthma. Allergy Asthma Proc. 2006;27:159–63.PubMedGoogle 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. Allergy. 2007;62:943–8.PubMedCrossRefGoogle Scholar
Eng PA, Borer-Reinhold M, Heijnen IAFM, Gnehm HPE. Twelve-year follow-up after discontinuation of preseasonal grass pollen immunotherapy in childhood. Allergy. 2006;61:198–201.PubMedCrossRefGoogle Scholar
Durham SR, Emminger W, Kapp A, Colombo G, de Monchy JG, Rak S, Scadding GK, Andersen JS, Riis B, Dahl R. 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 e1-7.PubMedCrossRefGoogle Scholar
Cox L, Jacobsen L. Comparison of allergen immunotherapy practice patterns in the United States and Europe. Ann Allergy Asthma Immunol. 2009;103:451–9. quiz 9-61, 95.PubMedCrossRefGoogle Scholar
• Senna G, Lombardi C, Canonica GW, Passalacqua G. How adherent to sublingual immunotherapy prescriptions are patients? The manufacturers' viewpoint. J Allergy Clin Immunol. 2010;126:668–9. Study demonstrates the relatively poor compliance with SLIT in ‘real-life’ studies
Hankin CS, Cox L, Lang D, et al. Allergy immunotherapy among Medicaid-enrolled children with allergic rhinitis: patterns of care, resource use, and costs. J Allergy Clin Immunol. 2008;121:227–32.PubMedCrossRefGoogle Scholar
Hsu NM, Reisacher WR. A comparison of attrition rates in patients undergoing sublingual immunotherapy vs subcutaneous immunotherapy. International forum of allergy & rhinology 2012;2:280–4.
• Pajno GB, Caminiti L, Crisafulli G, et al. Adherence to sublingual immunotherapy in preschool children. Pediatr Allergy Immunol. 2012;23:688–9. Demonstrates poor compliance with SLIT in the very young pediatric population
Pajno GB, Vita D, Caminiti L, et al. Children's compliance with allergen immunotherapy according to administration routes. J Allergy Clin Immunol. 2005;116:1380–1.PubMedCrossRefGoogle Scholar
Rotiroti G, Shamji M, Durham SR, Till SJ. Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses. J Allergy Clin Immunol. 2012;130:918–24 e1.PubMedCrossRefGoogle Scholar
Bal SM, Ding Z, van Riet E, Jiskoot W, Bouwstra JA. Advances in transcutaneous vaccine delivery: do all ways lead to Rome? Journal of controlled release. 2010;148:266–82.
Nestle FO, Di Meglio P, Qin JZ, Nickoloff BJ. Skin immune sentinels in health and disease. Nat Rev Immunol. 2009;9:679–91.PubMedGoogle Scholar
Bos JD, Meinardi MM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9:165–9.PubMedCrossRefGoogle Scholar
Matzinger P. Friendly and dangerous signals: is the tissue in control? Nat Immunol. 2007;8:11–3.PubMedCrossRefGoogle Scholar
Swamy M, Jamora C, Havran W, Hayday A. Epithelial decision makers: in search of the 'epimmunome'. Nat Immunol. 2010;11:656–65.PubMedCrossRefGoogle Scholar
Cevikbas F, Steinhoff M. IL-33: a novel danger signal system in atopic dermatitis. J Invest Dermatol. 2012;132:1326–9.PubMedCrossRefGoogle Scholar
Gilliet M, Soumelis V, Watanabe N, et al. Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells. J Exp Med. 2003;197:1059–63.PubMedCrossRefGoogle Scholar
Savinko T, Matikainen S, Saarialho-Kere U, et al. IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors. J Invest Dermatol. 2012;132:1392–400.PubMedCrossRefGoogle Scholar
Soumelis V. TSLP: from allergy to vaccine adjuvant. Eur J Immunol. 2012;42:293–5.PubMedCrossRefGoogle Scholar
Soumelis V, Reche PA, Kanzler H, et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol. 2002;3:673–80.PubMedCrossRefGoogle Scholar
Noon L. Prophylactic inoculation against hay fever. Lancet. 1911;1:1572–3.CrossRefGoogle Scholar
Scadding GK, Brostoff J. Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite. Clin Allergy. 1986;16:483–91.PubMedCrossRefGoogle Scholar
Tucker MH, Tankersley MS. Perception and practice of sublingual immunotherapy among practicing allergists. Ann Allergy Asthma Immunol. 2008;101:419–25.PubMedCrossRefGoogle Scholar
Sikora JM, Tankersley MS. Perception and practice of sublingual immunotherapy among practicing allergists in the United States. Ann Allergy Asthma Immunol 2013; in press.
Esch RE, Bush RK, Peden D, Lockey RF. Sublingual-oral administration of standardized allergenic extracts: phase 1 safety and dosing results. Ann Allergy Asthma Immunol. 2008;100:475–81.PubMedCrossRefGoogle Scholar
Skoner D, Gentile D, Bush R, Fasano MB, McLaughlin A, Esch RE. Sublingual immunotherapy in patients with allergic rhinoconjunctivitis caused by ragweed pollen. J Allergy Clin Immunol. 2010;125(3):660–6
Creticos P, Esch R, Couroux P, Gentile D, Angelo P, Whitlow B, et al. A Randomized, Double-Blind, Placebo-Controlled, Parallel Trial of Standardized Short Ragweed Sublingual Allergy Immunotherapy Liquid Extract in Adult Subjects with Ragweed-Induced Allergic Rhinoconjunctivitis. Journal of Allergy and Clinical Immunology. 2013;abstract in press.
Creticos P, Maloney J, Nolte H, Creticos P, Maloney J, Nolte H, et al. Efficacy and safety of a novel ragweed Allergy Immunotherapy Tablet (AIT) during peak season in North America. J Allerg Clin Immunol. 2012;129:AB143.CrossRefGoogle Scholar
Maloney J, Nolte H, Nekam K, et al. Dose-related effects of ragweed allergy immunotherapy tablet on nasal and ocular symptoms of allergic rhinoconjunctivitis during the peak ragweed pollen seasons in Europe and North America. J Allerg Clin Immunol. 2012;129:AB47.CrossRefGoogle Scholar
Blaiss M, Maloney J, Nolte H, Gawchik S, Yao R, Skoner DP. Efficacy and safety of timothy grass allergy immunotherapy tablets in North American children and adolescents. J Allergy Clin Immunol. 2011;127(64–71):e1–4.PubMedGoogle Scholar
Cox LS, Casale TB, Nayak AS, Bernstein DI, Creticos PS, Ambroisine L, et al. Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: The importance of allergen-specific serum IgE. J Allergy Clin Immunol. 2012;130(6):1327–34
Nelson HS, Nolte H, Creticos P, Maloney J, Wu J, Bernstein DI. Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults. J Allergy Clin Immunol. 2011;127(72–80):e1–2.Google Scholar
Amar SM, Harbeck RJ, Sills M, Silveira LJ, O'Brien H, Nelson HS. Response to sublingual immunotherapy with grass pollen extract: monotherapy versus combination in a multiallergen extract. J Allergy Clin Immunol. 2009;124(1):150–6. e1–5. Epub 2009/06/16.PubMedCrossRefGoogle Scholar
Swamy RS, Reshamwala N, Hunter T, Vissamsetti S, Santos CB, Baroody FM, et al. Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy. J Allergy Clin Immunol. 2012;130(1):215–24 e7ne
Bush RK, Swenson C, Fahlberg B, Evans MD, Esch R, Morris M, et al. House dust mite sublingual immunotherapy: results of a US trial. J Allergy Clin Immunol. 2011;127(4):974-81 e1–7.
Wood R. Immunologic effects of cockroach specific immunotherapy AAAAI annual meeting presentation. 2012.
Novak N. Allergen specific immunotherapy for atopic dermatitis. Curr Opin Allergy Clin Immunol. 2007;7:542–6.PubMedCrossRefGoogle Scholar
Bussmann C, Bockenhoff A, Henke H, Werfel T, Novak N. Does allergen-specific immunotherapy represent a therapeutic option for patients with atopic dermatitis? J Allergy Clin Immunol. 2006;118(6):1292–8.
•• Compalati E, Rogkakou A, Passalacqua G, Canonica GW. Evidences of efficacy of allergen immunotherapy in atopic dermatitis: an updated review. Curr Opin Allergy Clin Immunol. 2012;12:427–33. Systematic review of AIT for atopic dermatitis indicating that the data are conflicting in terms of the efficacy of this treatment for this condition and underscoring the need for further studies
Novak N, Thaci D, Hoffmann M, et al. Subcutaneous immunotherapy with a depigmented polymerized birch pollen extract–a new therapeutic option for patients with atopic dermatitis. Int Arch Allergy Immunol. 2011;155:252–6.PubMedCrossRefGoogle Scholar
Novak N, Bieber T, Hoffmann M, Folster-Holst R, Homey B, Werfel T, et al. Efficacy and safety of subcutaneous allergen-specific immunotherapy with depigmented polymerized mite extract in atopic dermatitis. J Allergy Clin Immunol. 2012;130(4):925–31
Pajno GB, Caminiti L, Vita D, et al. Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J Allergy Clin Immunol. 2007;120:164–70.PubMedCrossRefGoogle Scholar
Immune Tolerance Network. Promoting tolerance to common allergens in high-risk children: Global Prevention of Asthma in Children (GPAC) Study. ClinicalTrials.gov Identifier:NCT00346398.
Nelson HS, Lahr J, Rule R, Bock A, Leung D. Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract. J Allergy Clin Immunol. 1997;99:744–51.PubMedCrossRefGoogle Scholar
Oppenheimer JJ, Nelson HS, Bock SA, Christensen F, Leung DY. Treatment of peanut allergy with rush immunotherapy. J Allergy Clin Immunol. 1992;90:256–62.PubMedCrossRefGoogle Scholar
Patriarca C, Romano A, Venuti A, et al. Oral specific hyposensitization in the management of patients allergic to food. Allergol Immunopathol (Madr). 1984;12:275–81.Google Scholar
Patriarca G, Nucera E, Roncallo C, et al. Oral desensitizing treatment in food allergy: clinical and immunological results. Aliment Pharmacol Ther. 2003;17:459–65.PubMedCrossRefGoogle Scholar
Patriarca G, Buonomo A, Roncallo C, et al. Oral desensitisation in cow milk allergy: immunological findings. Int J Immunopathol Pharmacol. 2002;15:53–8.PubMedGoogle Scholar
Buchanan AD, Green TD, Jones SM, et al. Egg oral immunotherapy in nonanaphylactic children with egg allergy. J Allergy Clin Immunol. 2007;119:199–205.PubMedCrossRefGoogle Scholar
Vickery BP, Pons L, Kulis M, Steele P, Jones SM, Burks AW. Individualized IgE-based dosing of egg oral immunotherapy and the development of tolerance. Ann Allergy Asthma Immunol. 2010;105:444–50.PubMedCrossRefGoogle Scholar
Itoh N, Itagaki Y, Kurihara K. Rush specific oral tolerance induction in school-age children with severe egg allergy: one year follow up. Allergol Int. 2010;59:43–51.PubMedCrossRefGoogle Scholar
Garcia Rodriguez R, Urra JM, Feo-Brito F, et al. Oral rush desensitization to egg: efficacy and safety. Clin Exp Allergy. 2011;41:1289–96.PubMedCrossRefGoogle Scholar
Meglio P, Giampietro PG, Carello R, Gabriele I, Avitabile S, Galli E. Oral food desensitization in children with IgE-mediated hen's egg allergy: a new protocol with raw hen's egg. Pediatr Allergy Immunol. 2012 Aug 13.
Fuentes-Aparicio V, Alonso-Lebrero E, Zapatero L, Infante S, Lorente R, Angeles Munoz-Fernandez M, et al. Oral immunotherapy in hen's egg-allergic children increases a hypo-proliferative subset of CD4+ T cells that could constitute a marker of tolerance achievement. Pediatr Allergy Immunol. 2012;23(7):648–53.
Dello Iacono I, Tripodi S, Calvani M, Panetta V, Verga MC, Miceli Sopo S. Specific oral tolerance induction with raw hen's egg in children with very severe egg allergy: A randomized controlled trial. Pediatr Allergy Immunol. 2012 Sep 9.
•• Burks AW, Jones SM, Wood RA, et al. Oral immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012;367:233–43. Well-designed study examining the efficacy and safety of egg OIT, showing that most can be desensitized but most do not achieve long-term tolerance
Meglio P, Bartone E, Plantamura M, Arabito E, Giampietro PG. A protocol for oral desensitization in children with IgE-mediated cow's milk allergy. Allergy. 2004;59:980–7.PubMedCrossRefGoogle Scholar
Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007;62:1261–9.PubMedCrossRefGoogle Scholar
Staden U, Blumchen K, Blankenstein N, et al. Rush oral immunotherapy in children with persistent cow's milk allergy. J Allerg Clin Immunol. 2008;122:418–9.CrossRefGoogle Scholar
Longo G, Barbi E, Berti I, et al. Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol. 2008;121:343–7.PubMedCrossRefGoogle Scholar
Martorell Aragones A, Felix Toledo R, Cerda Mir JC, Martorell Calatayud A. Oral rush desensitization to cow milk. Following of desensitized patients during three years. Allergologia et Immunopathologia. 2007;35:174–6.PubMedCrossRefGoogle Scholar
Pajno GB, Caminiti L, Ruggeri P, et al. Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study. Ann Allergy Asthma Immunol. 2010;105:376–81.
Skripak JM, Nash SD, Rowley H, et al. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol. 2008;122:1154–60.PubMedCrossRefGoogle Scholar
Morisset M, Moneret-Vautrin DA, Guenard L, et al. Oral desensitization in children with milk and egg allergies obtains recovery in a significant proportion of cases. A randomized study in 60 children with cow's milk allergy and 90 children with egg allergy. Eur Ann Allergy Clin Immunol. 2007;39:12–9.PubMedGoogle Scholar
Zapatero L, Alonso E, Fuentes V, Martinez MI. Oral desensitization in children with cow's milk allergy. J Investig Allergol Clin Immunol. 2008;18:389–96.PubMedGoogle Scholar
•• Brozek JL, Terracciano L, Hsu J, et al. Oral immunotherapy for IgE-mediated cow's milk allergy: a systematic review and meta-analysis. Clin Exp Allergy. 2012;42:363–74. Systematic review that concluded that the “potentially large benefit of oral immunotherapy in patients with cow's milk allergy may be counterbalanced by frequent and sometimes serious adverse effects”
Clark AT, Islam S, King Y, Deighton J, Anagnostou K, Ewan PW. Successful oral tolerance induction in severe peanut allergy. Allergy. 2009;64:1218–20.PubMedCrossRefGoogle Scholar
Jones SM, Pons L, Roberts JL, et al. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009;124(292–300):e1–e97.Google Scholar
Blumchen K, Ulbricht H, Staden U, et al. Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol. 2010;126:83–91. e1.PubMedCrossRefGoogle Scholar
Anagnostou K, Clark A, King Y, Islam S, Deighton J, Ewan P. Efficacy and safety of high-dose peanut oral immunotherapy with factors predicting outcome. Clin Exp Allergy. 2011;41:1273–81.PubMedCrossRefGoogle Scholar
Varshney P, Jones SM, Scurlock AM, et al. A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol. 2011;127:654–60.PubMedCrossRefGoogle Scholar
•• Nurmatov U, Venderbosch I, Devereux G, Simons FE, Sheikh A. Allergen-specific oral immunotherapy for peanut allergy. Cochrane Database Syst Rev. 2012;9:CD009014. Systematic review that concluded that “in view of the risk of adverse events and the lack of evidence of long-term benefits, allergen-specific peanut OIT cannot currently be recommended as a treatment for the management of patients with IgE-mediated peanut allergy”
Thyagarajan A, Varshney P, Jones SM, et al. Peanut oral immunotherapy is not ready for clinical use. J Allergy Clin Immunol. 2010;126:31–2.PubMedCrossRefGoogle Scholar
• Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol. 2012;129:448–55. 55 e1–5. Review of AIT for milk allergy that concluded “OIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects. Clinical desensitization was lost in some cases within 1 week off therapy”
Enrique E, Pineda F, Malek T, et al. Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol. 2005;116:1073–9.PubMedCrossRefGoogle Scholar
Fernandez-Rivas M, Garrido Fernandez S, Nadal JA, et al. Randomized double-blind, placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract. Allergy. 2009;64:876–83.PubMedCrossRefGoogle Scholar
Kim EH, Bird JA, Kulis M, et al. Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization. J Allergy Clin Immunol. 2011;127:640–6.PubMedCrossRefGoogle Scholar
Kulis M, Saba K, Kim EH, et al. Increased peanut-specific IgA levels in saliva correlate with food challenge outcomes after peanut sublingual immunotherapy. J Allergy Clin Immunol. 2012;129:1159–62.PubMedCrossRefGoogle Scholar
Mauro M, Russello M, Incorvaia C, et al. Birch-apple syndrome treated with birch pollen immunotherapy. Int Arch Allergy Immunol. 2011;156:416–22.PubMedCrossRefGoogle Scholar
Nucera E, Aruanno A, Rizzi A, et al. Profilin desensitization in two patients with plant-derived food allergy. Int J Immunopathol Pharmacol. 2012;25:531–5.PubMedGoogle Scholar
Cortellini G, Spadolini I, Santucci A, et al. Improvement of shrimp allergy after sublingual immunotherapy for house dust mites: a case report. Eur Ann Allergy Clin Immunol. 2011;43:162–4.PubMedGoogle Scholar
Patriarca G, Nucera E, Roncallo C, et al. Sublingual desensitization in patients with wasp venom allergy: preliminary results. Int J Immunopathol Pharmacol. 2008;21:669–77.PubMedGoogle Scholar
Severino MG, Cortellini G, Bonadonna P, Francescato E, Panzini I, Macchia D, et al. Sublingual immunotherapy for large local reactions caused by honeybee sting: a double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2008;122(1):44–8.
Mitragotri S. Immunization without needles. Nat Rev Immunol. 2005;5:905–16.PubMedCrossRefGoogle Scholar
Frech SA, Dupont HL, Bourgeois AL, et al. Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled field trial. Lancet. 2008;371:2019–25.PubMedCrossRefGoogle Scholar
Frerichs DM, Ellingsworth LR, Frech SA, et al. Controlled, single-step, stratum corneum disruption as a pretreatment for immunization via a patch. Vaccine. 2008;26:2782–7.PubMedCrossRefGoogle Scholar
Sullivan SP, Koutsonanos DG, Del Pilar Martin M, Lee JW, Zarnitsyn V, Choi SO, et al. Dissolving polymer microneedle patches for influenza vaccination. Nat Med. 2010;16(8):915–20.
Enfield J, O'Connell ML, Lawlor K, Jonathan E, O'Mahony C, Leahy M. In-vivo dynamic characterization of microneedle skin penetration using optical coherence tomography. J Biomed Opt. 2010;15:046001.PubMedCrossRefGoogle Scholar
Fernando GJ, Chen X, Prow TW, et al. Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model. PLoS One. 2010;5:e10266.
Haq MI, Smith E, John DN, et al. Clinical administration of microneedles: skin puncture, pain and sensation. Biomed Microdevices. 2009;11:35–47.PubMedCrossRefGoogle Scholar
Kim YC, Jarrahian C, Zehrung D, Mitragotri S, Prausnitz MR. Delivery systems for intradermal vaccination. Curr Top Microbiol Immunol. 2012;351:77–112.PubMedCrossRefGoogle Scholar
van der Maaden K, Jiskoot W, Bouwstra J. Microneedle technologies for (trans)dermal drug and vaccine delivery. J Contr Rel Offic J Contr Rel Soc. 2012;161:645–55.CrossRefGoogle Scholar
Vrdoljak A, McGrath MG, Carey JB, et al. Coated microneedle arrays for transcutaneous delivery of live virus vaccines. J Contr Rel Offic J Contr Rel Soc. 2012;159:34–42.CrossRefGoogle Scholar
Wood LC, Jackson SM, Elias PM, Grunfeld C, Feingold KR. Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. J Clin Invest. 1992;90:482–7.PubMedCrossRefGoogle Scholar
Tan G, Xu P, Lawson LB, et al. Hydration effects on skin microstructure as probed by high-resolution cryo-scanning electron microscopy and mechanistic implications to enhanced transcutaneous delivery of biomacromolecules. J Pharm Sci. 2010;99:730–40.PubMedGoogle Scholar
Dupont C, Kalach N, Soulaines P, Legoue-Morillon S, Piloquet H, Benhamou PH. Cow's milk epicutaneous immunotherapy in children: a pilot trial of safety, acceptability, and impact on allergic reactivity. J Allergy Clin Immunol. 2010;125:1165–7.PubMedCrossRefGoogle Scholar
Mondoulet L, Dioszeghy V, Ligouis M, Dhelft V, Dupont C, Benhamou PH. Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy. Clin Exp Allergy. 2010;40:659–67.PubMedCrossRefGoogle Scholar
Eyler JM. Smallpox in history: the birth, death, and impact of a dread disease. J Lab Clin Med. 2003;142:216–20.PubMedCrossRefGoogle Scholar
Frech SA, Kenney RT, Spyr CA, et al. Improved immune responses to influenza vaccination in the elderly using an immunostimulant patch. Vaccine. 2005;23:946–50.PubMedCrossRefGoogle Scholar
Jodar L, Duclos P, Milstien JB, Griffiths E, Aguado MT, Clements CJ. Ensuring vaccine safety in immunization programmes–a WHO perspective. Vaccine. 2001;19:1594–605.PubMedCrossRefGoogle Scholar
Glenn GM, Kenney RT, Ellingsworth LR, Frech SA, Hammond SA, Zoeteweij JP. Transcutaneous immunization and immunostimulant strategies: capitalizing on the immunocompetence of the skin. Expert Rev Vaccines. 2003;2:253–67.PubMedCrossRefGoogle Scholar
Glenn GM, Rao M, Matyas GR, Alving CR. Skin immunization made possible by cholera toxin. Nature. 1998;391:851.PubMedCrossRefGoogle Scholar
Glenn GM, Scharton-Kersten T, Vassell R, Mallett CP, Hale TL, Alving CR. Transcutaneous immunization with cholera toxin protects mice against lethal mucosal toxin challenge. J Immunol. 1998;161:3211–4.PubMedGoogle Scholar
Glenn GM, Taylor DN, Li X, Frankel S, Montemarano A, Alving CR. Transcutaneous immunization: a human vaccine delivery strategy using a patch. Nat Med. 2000;6:1403–6.PubMedCrossRefGoogle Scholar
Phillips EW. Relief of hay-fever by intradermal injections of pollen extract. JAMA. 1926;86:182–4.CrossRefGoogle Scholar
Hurwitz SH. Medicine: seasonal hay fever-some problems in treatment. Cal West Med. 1930;33:520–1.PubMedGoogle Scholar
Vallery-Radot P, Hangenau J. Asthme d'origine équine. Essai de désensibilisation par des cutiréactions répétées. Bull Soc Méd Hôp Paris. 1921;45:1251–60.Google Scholar
Pautrizel R, Cabanieu G, Bricaud H, Broustet P. Allergenic group specificity & therapeutic consequences in asthma; specific desensitization method by epicutaneous route. Sem Hop. 1957;33:1394–403.PubMedGoogle Scholar
Blamoutier P, Blamoutier J, Guibert L. Treatment of pollinosis with pollen extracts by the method of cutaneous quadrille ruling. Presse Med. 1959;67:2299–301.PubMedGoogle Scholar
Blamoutier P, Blamoutier J, Guibert L. Traitement co-saisonnier de la pollinose par l'application d'extraits de pollens sur des quadrillages cutanés. Revue Francaise d'Allergie. 1961;1:112–20.CrossRefGoogle Scholar
Eichenberger H, Storck H. Co-seasonal desensitization of pollinosis with the scarification-method of Blamoutier. Acta Allergol. 1966;21:261–7.PubMedCrossRefGoogle Scholar
Martin-DuPan R, Buser F, Neyroud M. Treatment of pollen allergy using the cutaneous checker square method of Blamoutier and Guibert. Schweiz Rundsch Med Prax. 1971;60:1469–72.PubMedGoogle Scholar
Palma-Carlos A-G. Traitement co-saisonnier des pollinoses au Portugal par la méthode des quadrillages cutanés. Revue Francaise d'Allergie. 1967;7:92–5.CrossRefGoogle Scholar
Senti G, Graf N, Haug S, et al. Epicutaneous allergen administration as a novel method of allergen-specific immunotherapy. J Allergy Clin Immunol. 2009;124:997–1002.PubMedCrossRefGoogle Scholar
• Senti G, von Moos S, Tay F, et al. Epicutaneous allergen-specific immunotherapy ameliorates grass pollen-induced rhinoconjunctivitis: A double-blind, placebo-controlled dose escalation study. J Allergy Clin Immunol. 2012;129:128–35. EPIT dose-response study that demonstrated that EPIT can be effective in treating grass-induced allergic rhinitis
Agostinis F, Forti S, Di Berardino F. Grass transcutaneous immunotherapy in children with seasonal rhinoconjunctivitis. Allergy. 2010;65:410–1.PubMedCrossRefGoogle Scholar
Johansen P, Mohanan D, Martinez-Gomez JM, Kundig TM, Gander B. Lympho-geographical concepts in vaccine delivery. J Contr Rel Offic J Contr Rel Soc. 2010;148:56–62.CrossRefGoogle Scholar
Kündig TM, Johansen P, Senti G. Intralymphatic vaccination. In: Rapuolli R, Bagnoli F, editors. Vaccine design. Norfolk: Caister Academic Press; 2011. p. 211–24.Google Scholar
Senti G, Johansen P, Kundig TM. Intralymphatic immunotherapy. Curr Opin Allergy Clin Immunol. 2009;9:537–43.PubMedCrossRefGoogle Scholar
Senti G, Johansen P, Kundig TM. Intralymphatic immunotherapy: from the rationale to human applications. Curr Top Microbiol Immunol. 2011;352:71–84.PubMedCrossRefGoogle Scholar
von Moos S, Kundig TM, Senti G. Novel administration routes for allergen-specific immunotherapy: a review of intralymphatic and epicutaneous allergen-specific immunotherapy. Immunol Allergy Clin North Am. 2011;31(2):391–406.
Johansen P, Senti G, Martinez Gomez JM, et al. Toll-like receptor ligands as adjuvants in allergen-specific immunotherapy. Clin Exp Allergy. 2005;35:1591–8.PubMedCrossRefGoogle Scholar
Johansen P, Senti G, Martinez Gomez JM, Wuthrich B, Bot A, Kundig TM. Heat denaturation, a simple method to improve the immunotherapeutic potential of allergens. Eur J Immunol. 2005;35:3591–8.PubMedCrossRefGoogle Scholar
Martinez-Gomez JM, Johansen P, Erdmann I, Senti G, Crameri R, Kundig TM. Intralymphatic injections as a new administration route for allergen-specific immunotherapy. Int Arch Allergy Immunol. 2009;150:59–65.PubMedCrossRefGoogle Scholar
Martinez-Gomez JM, Johansen P, Rose H, et al. Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy. Allergy. 2009;64:172–8.PubMedCrossRefGoogle Scholar
Mohanan D, Slutter B, Henriksen-Lacey M, et al. Administration routes affect the quality of immune responses: a cross-sectional evaluation of particulate antigen-delivery systems. J Contr Rel Offic J Contr Rel Soc. 2010;147:342–9.CrossRefGoogle Scholar
Senti G, Prinz Vavricka BM, Erdmann I, et al. Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc Natl Acad Sci U S A. 2008;105:17908–12.PubMedCrossRefGoogle Scholar
Malling H, Blom L, Poulsen B, Poulsen L, Witten M. Is intralymphatic specific immunotherapy with grass pollen allergen ready for clinical use? European Academy of Allergy and Clinical Immunology Congress; Geneva. http://www.eaaci2012.com/SiteSpecific/Eaaci2012/AbstractDetails.aspx?Nr=1595
Siegrist CA. The immunology of vaccination. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 5th ed. Philadelphia: Elsevier Inc; 2008. p. 17–36.Google Scholar
Hylander T, Latif L, Petersson-Westin U, Cardell LO. Intralymphatic allergen-specific immunotherapy: an effective and safe alternative treatment route for pollen-induced allergic rhinitis. J Allergy Clin Immunol; 2013: in press.
• Senti G, Crameri R, Kuster D, et al. Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections. J Allergy Clin Immunol. 2012;129:1290–6. Demonstrated the effectiveness of ILIT in treating cat allergy
Bolhaar ST, Zuidmeer L, Ma Y, et al. A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebocontrolled food challenge. Clin Exp Allergy 2005;35:1638–44.
Burks AW, King N, Bannon GA. Modification of a major peanut allergen leads to loss of IgE binding. Int Arch Allergy Immunol 1999;118:313–4.
Drew AC, Eusebius NP, Kenins L, et al. Hypoallergenic variants of the major latex allergen Hev b 6.01 retaining human T lymphocyte reactivity. J Immunol 2004;173:5872–9.
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 1998;12:231–42.
Ferreira F, Rohlfs A, Hoffmann-Sommergruber K, et al. Modulation of IgE-binding properties of tree pollen allergens by site-directed mutagenesis. Adv Exp Med Biol. 1996;409:127–35.PubMedCrossRefGoogle Scholar
Okada T, Swoboda I, Bhalla PL, Toriyama K, Singh MB. Engineering of hypoallergenic mutants of the Brassica pollen allergen, Bra r 1, for immunotherapy. FEBS Lett 1998;434:255–60.
Rabjohn P, West CM, Connaughton C, et al. Modification of peanut allergen Ara h 3: effects on IgE binding and T cell stimulation. Int Arch Allergy Immunol 2002;128:15–23.
Stanley JS, King N, Burks AW, et al. Identification and mutational analysis of the immunodominant IgE binding epitopes of the major peanut allergen Ara h 2. Archives of biochemistry and biophysics 1997;342:244–53.
Swoboda I, Bugajska-Schretter A, Linhart B, et al. A recombinant hypoallergenic parvalbumin mutant for immunotherapy of IgE-mediated fish allergy. J Immunol 2007;178:6290–6.
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 2002;32:270–80.
Niederberger V, Horak F, Vrtala S, 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, 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.
Focke-Tejkl M, Valenta R. Safety of engineered allergen-specific immunotherapy vaccines. Curr Opin Allergy Clin Immunol 2012;12:555–63.
Larche M. Immunoregulation by targeting T cells in the treatment of allergy and asthma. Curr Opin Immunol 2006;18:745–50.
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;116:608–13.PubMedCrossRefGoogle 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. 2008;122:951–60.PubMedCrossRefGoogle Scholar
Vrtala S, Hirtenlehner K, Susani M, Akdis M, Kussebi F, Akdis CA, et al. Genetic engineering of a hypoallergenic trimer of the major birch pollen allergen Bet v 1. FASEB J. 2001;15(11):2045–7.
Vrtala S, Hirtenlehner K, Vangelista L, et al. Conversion of the major birch pollen allergen, Bet v 1, into two nonanaphylactic T cell epitope-containing fragments: candidates for a novel form of specific immunotherapy. J Clin Invest. 1997;99:1673–81.PubMedCrossRefGoogle Scholar
Egger C, Horak F, Vrtala S, Valenta R, Niederberger V. Nasal application of rBet v 1 or non-IgE-reactive T-cell epitope-containing rBet v 1 fragments has different effects on systemic allergen-specific antibody responses. J Allergy Clin Immunol. 2010;126:1312–5. e4.PubMedCrossRefGoogle Scholar
Pree I, Shamji MH, Kimber I, Valenta R, Durham SR, Niederberger V. Inhibition of CD23-dependent facilitated allergen binding to B cells following vaccination with genetically modified hypoallergenic Bet v 1 molecules. Clin Exp Allergy. 2010;40:1346–52.PubMedCrossRefGoogle 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. 2005;116:347–54.PubMedCrossRefGoogle 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. 2005;138:59–66.PubMedCrossRefGoogle 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 Allergy. 2008;38:1514–25.PubMedCrossRefGoogle Scholar
van Hage-Hamsten M, Kronqvist M, Zetterstrom O, et al. Skin test evaluation of genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1: results obtained with a mix of two recombinant Bet v 1 fragments and recombinant Bet v 1 trimer in a Swedish population before the birch pollen season. J Allergy Clin Immunol 1999;104:969–77.
Niederberger V, Reisinger J, Valent P, Krauth MT, Pauli G, van Hage M, et al. Vaccination with genetically modified birch pollen allergens: immune and clinical effects on oral allergy syndrome. J Allergy Clin Immunol. 2007;119(4):1013–6.
Kundig TM, Senti G, Schnetzler G, et al. Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults. J Allergy Clin Immunol. 2006;117:1470–6.PubMedCrossRefGoogle Scholar
• Senti G, Johansen P, Haug S, et al. Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial. Clin Exp Allergy. 2009;39:562–70. Study evaluated a virus-like particle as an adjuvant for dust mite AIT.
Djurup R, Malling HJ. High IgG4 antibody level is associated with failure of immunotherapy with inhalant allergens. Clin Allergy. 1987;17:459–68.PubMedCrossRefGoogle Scholar
Edlmayr J, Niespodziana K, Linhart B, et al. A combination vaccine for allergy and rhinovirus infections based on rhinovirus-derived surface protein VP1 and a nonallergenic peptide of the major timothy grass pollen allergen Phl p 1. J Immunol. 2009;182:6298–306.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
Norman PS, Ohman Jr JL, Long AA, et al. Treatment of cat allergy with T-cell reactive peptides. Am J Respir Crit Care Med. 1996;154:1623–8.PubMedGoogle Scholar
Pene J, Desroches A, Paradis L, 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.PubMedCrossRefGoogle Scholar
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.PubMedCrossRefGoogle Scholar
Haselden BM, Kay AB, Larche M. Immunoglobulin E-independent major histocompatibility complex-restricted T cell peptide epitope-induced late asthmatic reactions. J Exp Med. 1999;189:1885–94.PubMedCrossRefGoogle Scholar
Haselden BM, Syrigou E, Jones M, et al. Proliferation and release of IL-5 and IFN-gamma by peripheral blood mononuclear cells from cat-allergic asthmatics and rhinitics, non-cat-allergic asthmatics, and normal controls to peptides derived from Fel d 1 chain 1. J Allergy Clin Immunol. 2001;108:349–56.PubMedCrossRefGoogle 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. Allergy. 2005;60:1269–74.PubMedCrossRefGoogle Scholar
Alexander C, Ying S, A BK, Larche 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(1):52–8.
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. 2001;167:1734–9.PubMedGoogle 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. Lancet. 2002;360:47–53.PubMedCrossRefGoogle 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. Allergy. 2004;59:1097–101.PubMedCrossRefGoogle Scholar
Verhoef A, Alexander C, Kay AB, Larche M. T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity. PLoS Med. 2005;2:e78.PubMedCrossRefGoogle Scholar
Campbell JD, Buckland KF, McMillan SJ, 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.PubMedCrossRefGoogle Scholar
• Worm M, Lee HH, Kleine-Tebbe J, et al. Development and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy. J Allergy Clin Immunol. 2011;127:89–97. e1–14. Demonstrated that one administration of aT cell epitope vaccine suppressed late-phase skin reactions
• Patel D, Couroux P, Hickey P, 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. J Allergy Clin Immunol 2012. Demonstrates the efficacy andsafety of petide immunotherapy with a modified cat vaccine.
Horak F, Zieglmayer P, Zieglmayer R, et al. Early onset of action of a 5-grass-pollen 300-IR sublingual immunotherapy tablet evaluated in an allergen challenge chamber. J Allergy Clin Immunol. 2009;124:471–7. 7 e1.PubMedCrossRefGoogle Scholar
Berkowitz RB, Braker S, Lutz C, et al. Efficacy of fexofenadine in the prophylactic control of cat allergen-induced allergic rhinitis. Ann Allergy Asthma Immunol. 2006;96:327–33.PubMedCrossRefGoogle Scholar
Carballido JM, Carballido-Perrig N, Kagi MK, et al. T cell epitope specificity in human allergic and nonallergic subjects to bee venom phospholipase A2. J Immunol 1993;150:3582–91.
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. 1998;101:747–54.PubMedCrossRefGoogle Scholar
Texier C, Pouvelle S, Busson M, et al. HLA-DR restricted peptide candidates for bee venom immunotherapy. J Immunol. 2000;164:3177–84.PubMedGoogle Scholar
Tarzi M, Klunker S, Texier C, et al. Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy. Clin Exp Allergy. 2006;36:465–74.PubMedCrossRefGoogle Scholar
de Boissieu D, Dupont C. Sublingual immunotherapy for cow's milk protein allergy: a preliminary report. Allergy. 2006;61:1238–9.PubMedCrossRefGoogle Scholar