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Review

Allergen immunotherapy: progress and future outlook

, , , , &
Pages 745-769 | Received 04 Mar 2023, Accepted 27 Apr 2023, Published online: 05 May 2023

References

  • Galli SJ, Tsai M, Piliponsky AM. The development of allergic inflammation. Nature. 2008;454:445–454.
  • Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol. 2021;21:739–751.
  • Pawankar RC, Holgate ST, Lockey RF, et al. The WAO white book on allergy. 2013.
  • Pawankar R. Allergic diseases and asthma: a global public health concern and a call to action. World Allergy Organ J. 2014;7:12.
  • Gupta RS, Springston EE, Warrier MR, et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;128:e9–17.
  • Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al. The international EAACI/GA2 LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022;77:734–766.
  • Weidinger S, Beck LA, Bieber T, et al. Atopic dermatitis. Nat Rev Dis Primers. 2018;4:1.
  • Sturm GJ, Varga EM, Roberts G, et al. EAACI guidelines on allergen immunotherapy: hymenoptera venom allergy. Allergy. 2018;73:744–764.
  • Motosue MS, Bellolio MF, Van Houten HK, et al. Increasing emergency department visits for anaphylaxis, 2005-2014. J Allergy Clin Immunol Pract. 2017;5:171–175.
  • Turner PJ, Gowland MH, Sharma V, et al. Increase in anaphylaxis-related hospitalizations but no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992-2012. J Allergy Clin Immunol. 2015;135:956–963.
  • Motosue MS, Bellolio MF, Van Houten HK, et al. Outcomes of emergency department anaphylaxis visits from 2005 to 2014. J Allergy Clin Immunol Pract. 2018;6:1002–1009.
  • Jeppesen AN, Christiansen CF, Frøslev T, et al. Hospitalization rates and prognosis of patients with anaphylactic shock in Denmark from 1995 through 2012. J Allergy Clin Immunol. 2016;137:1143–1147.
  • Liew WK, Williamson E, Tang ML. Anaphylaxis fatalities and admissions in Australia. J Allergy Clin Immunol. 2009;123:434–442.
  • Ma L, Danoff TM, Borish L. Case fatality and population mortality associated with anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133:1075–1083.
  • Mullins RJ, Dear KB, Tang ML. Time trends in Australian hospital anaphylaxis admissions in 1998-1999 to 2011-2012. J Allergy Clin Immunol. 2015;136:367–375.
  • Tejedor-Alonso MA, Moro-Moro M, Mosquera González M, et al. Increased incidence of admissions for anaphylaxis in Spain 1998-2011. Allergy. 2015;70:880–883.
  • Turner PJ, Campbell DE, Motosue MS, et al. Global trends in anaphylaxis epidemiology and clinical implications. J Allergy Clin Immunol Pract. 2020;8:1169–1176.
  • Mullins RJ, Wainstein BK, Barnes EH, et al. Increases in anaphylaxis fatalities in Australia from 1997 to 2013. Clin Exp Allergy. 2016;46:1099–1110.
  • Parrish CP, Kim H. Food-induced anaphylaxis: an update. Curr Allergy Asthma Rep. 2018;18:41.
  • Anagnostou K. Anaphylaxis in children: epidemiology, risk factors and management. Curr Pediatr Rev. 2018;14:180–186.
  • Protudjer JLP, Olén O, Vetander M, et al. Milk- related symptoms and immunoglobulin E reactivity in Swedish children from early life to adolescence. Nutrients. 2018;10. DOI:10.3390/nu10050651
  • Jackson CM, Kaplan AN, Järvinen KM. Environmental exposures may hold the key; impact of air pollution, greenness, and rural/farm lifestyle on allergic outcomes. Curr Allergy Asthma Rep. 2023;23:77–91.
  • Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299:1259–1260.
  • Renz H, Skevaki C. Early life microbial exposures and allergy risks: opportunities for prevention. Nat Rev Immunol. 2021;21:177–191. DOI:10.1038/s41577-020-00420-y
  • Rook GA, Adams V, Hunt J, et al. Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders. Springer Semin Immunopathol. 2004;25:237–255.
  • Haahtela T. A biodiversity hypothesis. Allergy. 2019;74:1445–1456.
  • Baloh CH, Mathias RA. Recent progress in the genetic and epigenetic underpinnings of atopy. J Allergy Clin Immunol. 2023;151:60–69. DOI:10.1016/j.jaci.2022.10.027
  • Coombs PR, Gell PG. Classification of Allergic Reactions Responsible for Clinical Hypersensitivity and Disease. In: Gell RR editor. Clinical Aspects of Immunology. Oxford: Oxford University Press; 1968. p. 575–596.
  • Abbas M, Moussa M, Akel H. Type I hypersensitivity reaction. StatPearls. Treasure Island (FL): StatPearls Publishing LLC; 2020.
  • Alvaro-Lozano M, Akdis CA, Akdis M, et al. EAACI allergen immunotherapy user’s guide. Pediatr Allergy Immunol. 2020;31(25):1–101. DOI:10.1111/pai.13189
  • Kucuksezer UC, Ozdemir C, Akdis M, et al. Precision/Personalized medicine in allergic diseases and asthma. Arch Immunol Ther Exp (Warsz). 2018;66:431–442.
  • Dong H, Hao Y, Li W, et al. IL-36 cytokines: their roles in asthma and potential as a therapeutic. Front Immunol. 2022;13:921275.
  • Halken S, Larenas-Linnemann D, Roberts G, et al. EAACI guidelines on allergen immunotherapy: prevention of allergy. Pediatr Allergy Immunol. 2017;28:728–745. DOI:10.1111/pai.12807
  • Kristiansen M, Dhami S, Netuveli G, et al. Allergen immunotherapy for the prevention of allergy: a systematic review and meta-analysis. Pediatr Allergy Immunol. 2017;28:18–29.
  • Graversen JH, Madsen M, Moestrup SK. CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma. Int J Biochem Cell Biol. 2002;34:309–314.
  • Pascual G, Glass CK. Nuclear receptors versus inflammation: mechanisms of transrepression. Trends Endocrinol Metab. 2006;17:321–327.
  • Kortekaas Krohn I, Callebaut I, Alpizar YA, et al. MP29-02 reduces nasal hyperreactivity and nasal mediators in patients with house dust mite-allergic rhinitis. Allergy. 2018;73:1084–1093.
  • Okano M. Mechanisms and clinical implications of glucocorticosteroids in the treatment of allergic rhinitis. Clin Exp Immunol. 2009;158:164–173.
  • (GINA) GIfA. Global strategy for asthma management and prevention 2021 [cited 2023 Jan 5]. Available from: https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf
  • Eraso I, Sangiovanni S, Morales EI, et al. Aspirin desensitization in NSAID-exacerbated respiratory disease and its outcomes in the clinical course of asthma: a systematic review of the literature and meta-analysis. PLoS ONE. 2021;16:e0247871.
  • Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated International consensus diagnostic criteria for eosinophilic esophagitis: proceedings of the AGREE conference. Gastroenterology. 2018;155:1022–33.e10.
  • Aceves SS, Alexander JA, Baron TH, et al. Endoscopic approach to eosinophilic esophagitis: American Society for gastrointestinal endoscopy consensus conference. Gastrointest Endosc. 2022;96:576–92.e1.
  • Hirano I, Chan ES, Rank MA, et al. AGA institute and the joint task force on allergy-immunology practice parameters clinical guidelines for the management of eosinophilic esophagitis. Annals of Allergy, Asthma & Immunol. 2020;124:416–423.
  • Kettner L, Seitl I, Fischer L. Recent advances in the application of microbial diamine oxidases and other histamine-oxidizing enzymes. World J Microbiol Biotechnol. 2022;38:232.
  • Muraro A, Worm M, Alviani C, et al. EAACI guidelines: anaphylaxis (2021 update). Allergy. 2022;77:357–377.
  • Agache I, Beltran J, Akdis C, et al. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI guidelines - recommendations on the use of biologicals in severe asthma. Allergy. 2020;75:1023–1042.
  • Agache I, Akdis CA, Akdis M, et al. EAACI biologicals guidelines-omalizumab for the treatment of chronic spontaneous urticaria in adults and in the paediatric population 12-17 years old. Allergy. 2022;77:17–38.
  • CM J, Miller C, Senior B. Management of chronic rhinosinusitis with nasal polyposis in the Era of biologics. J Asthma Allergy. 2021;14:873–882.
  • Humbert M, Busse W, Hanania NA, et al. Omalizumab in asthma: an update on recent developments. J Allergy Clin Immunol Pract. 2014;2:525–36.e1.
  • Segal M, Stokes JR, Casale TB. Anti-immunoglobulin e therapy. World Allergy Organ J. 2008;1:174–183.
  • Austin CD, Gonzalez Edick M, Ferrando RE, et al. A randomized, placebo-controlled trial evaluating effects of lebrikizumab on airway eosinophilic inflammation and remodelling in uncontrolled asthma (CLAVIER). Clin Exp Allergy. 2020;50:1342–1351.
  • Agache I, Akdis CA, Akdis M, et al. EAACI biologicals guidelines-recommendations for severe asthma. Allergy. 2021;76:14–44.
  • Maurer M, Khan DA, Elieh Ali Komi D, et al. Biologics for the use in chronic spontaneous Urticaria: when and which. J Allergy Clin Immunol Pract. 2021;9:1067–1078.
  • Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378:2486–2496.
  • Beck LA, Thaçi D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130–139.
  • Agache I, Akdis CA, Akdis M, et al. EAACI biologicals guidelines-dupilumab for children and adults with moderate-to-severe atopic dermatitis. Allergy. 2021;76:988–1009.
  • El-Qutob D. Off-label uses of omalizumab. Clin Rev Allergy Immunol. 2016;50:84–96.
  • Muñoz-Bellido FJ, Moreno E, Dávila I. Dupilumab: a review of present indications and off-label uses. J Investig Allergol Clin Immunol. 2022;32:97–115.
  • Gauvreau GM, O’Byrne PM, Boulet LP, et al. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N Engl J Med. 2014;370:2102–2110.
  • Corren J, Ambrose CS, Sałapa K, et al. Efficacy of tezepelumab in patients with severe, uncontrolled asthma and perennial allergy. J Allergy Clin Immunol Pract. 2021;9:4334–42.e6.
  • Dhami S, Kakourou A, Asamoah F, et al. Allergen immunotherapy for allergic asthma: a systematic review and meta-analysis. Allergy. 2017;72:1825–1848. DOI:10.1111/all.13208
  • Dhami S, Nurmatov U, Arasi S, et al. Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta-analysis. Allergy. 2017;72:1597–1631. DOI:10.1111/all.13201
  • Dhami S, Zaman H, Varga EM, et al. Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis. Allergy. 2017;72:342–365. DOI:10.1111/all.13077
  • Domdey A, Njue A, Nuabor W, et al. Allergy immunotherapies for allergic rhinitis: systematic review and assessment of evolving quality. Eur Ann Allergy Clin Immunol. 2019;51:147–158. DOI:10.23822/EurAnnACI.1764-1489.100
  • Roberts G, Pfaar O, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: allergic rhinoconjunctivitis. Allergy. 2018;73:765–798.
  • Walker SM, Durham SR, Till SJ, et al. Immunotherapy for allergic rhinitis. Clin Exp Allergy. 2011;41:1177–1200.
  • Pfaar O, Ankermann T, Augustin M, et al. Guideline on allergen immunotherapy in IgE-mediated allergic diseases: s2K guideline of the German Society of Allergology and Clinical Immunology (DGAKI), Society of Pediatric Allergology and Environmental Medicine (GPA), Medical Association of German Allergologists (AeDA), Austrian Society of Allergology and Immunology (ÖGAI), Swiss Society for Allergology and Immunology (SSAI), German Dermatological Society (DDG), German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), German Society of Pediatrics and Adolescent Medicine (DGKJ), Society of Pediatric Pulmonology (GPP), German Respiratory Society (DGP), German Professional Association of Otolaryngologists (BVHNO), German Association of Paediatric and Adolescent Care Specialists (BVKJ), Federal Association of Pneumologists, Sleep and Respiratory Physicians (BdP), Professional Association of German Dermatologists (BVDD). Allergol Select. 2022;6:167–232.
  • Tie K, Miller C, Zanation AM, et al. Subcutaneous versus sublingual immunotherapy for adults with allergic rhinitis: a systematic review with meta-analyses. Laryngoscope. 2021;132:499–508.
  • Meadows A, Kaambwa B, Novielli N, et al. A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis. Health Technol Assess. 2013;17:1–322.
  • Boldovjakova D, Cordoni S, Fraser CJ, et al. Sublingual immunotherapy vs placebo in the management of grass pollen-induced allergic rhinitis in adults: a systematic review and meta-analysis. Clin Otolaryngol. 2021;46:52–59.
  • Blanco C, Bazire R, Argiz L, et al. Sublingual allergen immunotherapy for respiratory allergy: a systematic review. Drugs Context. 2018;7:212552.
  • Agache I, Lau S, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: house dust mite-driven allergic asthma. Allergy. 2019;74:855–873.
  • Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127:S1–55.
  • Creticos PS, Bernstein DI, Casale TB, et al. Coseasonal initiation of allergen immunotherapy: a systematic review. J Allergy Clin Immunol Pract. 2016;4:1194–204.e4.
  • 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. 2006;355:1445–1455.
  • Bonifazi F, Jutel M, Biló BM, et al. Prevention and treatment of hymenoptera venom allergy: guidelines for clinical practice. Allergy. 2005;60:1459–1470.
  • Patrawala M, Shih J, Lee G, et al. Peanut oral immunotherapy: a current perspective. Curr Allergy Asthma Rep. 2020;20:14. DOI:10.1007/s11882-020-00908-6
  • Vickery BP, Vereda A, Casale TB, et al. AR101 oral immunotherapy for peanut allergy. N Engl J Med. 2018;379:1991–2001.
  • Nurmatov U, Dhami S, Arasi S, et al. Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis. Allergy. 2017;72:1133–1147. DOI:10.1111/all.13124
  • Gueguen C, Bouley J, Moussu H, et al. Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy. J Allergy Clin Immunol. 2016;137:545–558.
  • Zimmer A, Bouley J, Le Mignon M, et al. A regulatory dendritic cell signature correlates with the clinical efficacy of allergen-specific sublingual immunotherapy. J Allergy Clin Immunol. 2012;129:1020–1030.
  • Akdis CA, Blesken T, Akdis M, et al. Role of interleukin 10 in specific immunotherapy. J Clin Invest. 1998;102:98–106.
  • 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. 2008;121:1120–5.e2.
  • Bohle B, Kinaciyan T, Gerstmayr M, et al. Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation. J Allergy Clin Immunol. 2007;120:707–713.
  • O’Hehir RE, Gardner LM, de Leon MP, et al. House dust mite sublingual immunotherapy: the role for transforming growth factor-beta and functional regulatory T cells. Am J Respir Crit Care Med. 2009;180:936–947.
  • Shamji MH, Layhadi JA, Achkova D, et al. Role of IL-35 in sublingual allergen immunotherapy. J Allergy Clin Immunol. 2019;143:1131–1142.
  • Larché M, Akdis CA, Valenta R. Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol. 2006;6:761–771. DOI:10.1038/nri1934
  • van der Heijden FL, van Neerven RJ J, van Katwijk M, et al. Serum-IgE-facilitated allergen presentation in atopic disease. J Immunol. 1993;150:3643–3650.
  • Würtzen PA, Lund G, Lund K, et al. A double-blind placebo-controlled birch allergy vaccination study II: correlation between inhibition of IgE binding, histamine release and facilitated allergen presentation. Clin Exp Allergy. 2008;38:1290–1301.
  • Hamid QA, Schotman E, Jacobson MR, et al. Increases in IL-12 messenger RNA+ cells accompany inhibition of allergen-induced late skin responses after successful grass pollen immunotherapy. J Allergy Clin Immunol. 1997;99:254–260.
  • van de Veen W, Stanic B, Yaman G, et al. IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses. J Allergy Clin Immunol. 2013;131:1204–1212.
  • Boonpiyathad T, van de Veen W, Wirz O, et al. Role of Der p 1-specific B cells in immune tolerance during 2 years of house dust mite-specific immunotherapy. J Allergy Clin Immunol. 2019;143:1077–86.e10.
  • Lao-Araya M, Steveling E, Scadding GW, et al. Seasonal increases in peripheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol. 2014;134:1193–1195.
  • Golebski K, Layhadi JA, Sahiner U, et al. Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response. Immunity. 2021;54:291–307.e7.
  • Yepes-Nuñez JJ, Guyatt GH, Gómez-Escobar LG, et al. Allergen immunotherapy for atopic dermatitis: systematic review and meta-analysis of benefits and harms. J Allergy Clin Immunol. 2023;151:147–158.
  • Boyle RJ, Elremeli M, Hockenhull J, et al. Venom immunotherapy for preventing allergic reactions to insect stings. Cochrane Database Syst Rev. 2012;10:Cd008838.
  • Mosbech H, Deckelmann R, de Blay F, et al. Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2014;134:568–575.
  • Virchow JC, Backer V, Kuna P, et al. Efficacy of a house dust mite sublingual allergen immunotherapy tablet in adults with allergic asthma: a randomized clinical trial. JAMA. 2016;315:1715–1725.
  • Durham SR, Walker SM, Varga EM, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999;341:468–475.
  • Bozek A, Cudak A, Walter Canonica G. Long-term efficacy of injected allergen immunotherapy for treatment of grass pollen allergy in elderly patients with allergic rhinitis. Allergy Asthma Proc. 2020;41:271–277.
  • Penagos M, Durham SR. Allergen immunotherapy for long-term tolerance and prevention. J Allergy Clin Immunol. 2022;149:802–811. DOI:10.1016/j.jaci.2022.01.007
  • Chu DK, Wood RA, French S, et al. Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety. Lancet. 2019;393:2222–2232. DOI:10.1016/S0140-6736(19)30420-9
  • Food and Drug Administration, HHS. International conference on harmonisation; guidance on E15 pharmacogenomics definitions and sample coding; availability. Notice Fed Regist. 2008;73:19074–19076.
  • López JF, Bel Imam M, Satitsuksanoa P, et al. Mechanisms and biomarkers of successful allergen-specific immunotherapy. Asia Pac Allergy. 2022;12:e45.
  • Shamji MH, Kappen JH, Akdis M, et al. Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI position paper. Allergy. 2017;72:1156–1173. DOI:10.1111/all.13138
  • Breiteneder H, Peng YQ, Agache I, et al. Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma. Allergy. 2020;75:3039–3068.
  • Jakwerth CA, Kitzberger H, Pogorelov D, et al. Role of microRnas in type 2 diseases and allergen-specific immunotherapy. Front Allergy. 2022;3:993937.
  • Di Lorenzo G, Mansueto P, Pacor ML, et al. Evaluation of serum s-IgE/total IgE ratio in predicting clinical response to allergen-specific immunotherapy. J Allergy Clin Immunol. 2009;123:1103–1110.
  • Nogami K, Nagao M, Takase T, et al. House dust mite subcutaneous immunotherapy and lung function trajectory in children and adolescents with asthma. Children (Basel). 2022;9:487.
  • Floch V BL, Berjont N, Batard T, et al. Coordinated IgG2 and IgE responses as a marker of allergen immunotherapy efficacy. Allergy. 2022;77:1263–1273.
  • Heeringa JJ, McKenzie CI, Varese N, et al. Induction of IgG(2) and IgG(4) B-cell memory following sublingual immunotherapy for ryegrass pollen allergy. Allergy. 2020;75:1121–1132.
  • 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 Allergy. 2003;33:1198–1208.
  • Bianchini R, Karagiannis SN, Jordakieva G, et al. The Role of IgG4 in the fine tuning of tolerance in IgE-mediated allergy and cancer. Int J Mol Sci. 2020:21. DOI:10.3390/ijms21145017
  • Nikolov G, Todordova Y, Emilova R, et al. Allergen-specific IgE and IgG4 as biomarkers for immunologic changes during subcutaneous allergen immunotherapy. Antibodies (Basel). 2021;10:49.
  • James LK, Till SJ. Potential mechanisms for IgG4 inhibition of immediate hypersensitivity reactions. Curr Allergy Asthma Rep. 2016;16:23.
  • Gehlhar K, Schlaak M, Becker W, et al. Monitoring allergen immunotherapy of pollen-allergic patients: the ratio of allergen-specific IgG4 to IgG1 correlates with clinical outcome. Clin Exp Allergy. 1999;29:497–506. DOI:10.1046/j.1365-2222.1999.00525.x
  • Gómez E, Fernández TD, Doña I, et al. Initial immunological changes as predictors for house dust mite immunotherapy response. Clin Exp Allergy. 2015;45:1542–1553.
  • Yang L, Yang Y, Xu Q, et al. Specific IgE and IgG4 profiles of house dust mite components in allergen-specific immunotherapy. Front Immunol. 2021;12:786738.
  • Li Q, Li M, Yue W, et al. Predictive factors for clinical response to allergy immunotherapy in children with asthma and rhinitis. Int Arch Allergy Immunol. 2014;164:210–217.
  • Van Overtvelt L, Baron-Bodo V, Horiot S, et al. Changes in basophil activation during grass-pollen sublingual immunotherapy do not correlate with clinical efficacy. Allergy. 2011;66:1530–1537.
  • Eifan AO, Akkoc T, Yildiz A, et al. Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Clin Exp Allergy. 2010;40:922–932.
  • Shamji MH, Kappen J, Abubakar-Waziri H, et al. Nasal allergen-neutralizing IgG(4) antibodies block IgE-mediated responses: novel biomarker of subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol. 2019;143:1067–1076.
  • Shamji MH, Francis JN, Würtzen PA, et al. Cell-free detection of allergen-IgE cross-linking with immobilized phase CD23: inhibition by blocking antibody responses after immunotherapy. J Allergy Clin Immunol. 2013;132:1003–1005.
  • Shamji MH, Wilcock LK, Wachholz PA, et al. The IgE-facilitated allergen binding (FAB) assay: validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses. J Immunol Methods. 2006;317:71–79.
  • Schroeder JT, Kagey-Sobotka A, Lichtenstein LM. The role of the basophil in allergic inflammation. Allergy. 1995;50:463–472.
  • MacGlashan D Jr. Expression of CD203c and CD63 in human basophils: relationship to differential regulation of piecemeal and anaphylactic degranulation processes. Clin Exp Allergy. 2010;40:1365–1377.
  • Hoffmann HJ, Santos AF, Mayorga C, et al. The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease. Allergy. 2015;70:1393–1405. DOI:10.1111/all.12698
  • Chinthrajah RS, Purington N, Andorf S, et al. Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2019;394:1437–1449.
  • Caruso M, Cibella F, Emma R, et al. Basophil biomarkers as useful predictors for sublingual immunotherapy in allergic rhinitis. Int Immunopharmacol. 2018;60:50–58.
  • Patil SU, Steinbrecher J, Calatroni A, et al. Early decrease in basophil sensitivity to Ara h 2 precedes sustained unresponsiveness after peanut oral immunotherapy. J Allergy Clin Immunol. 2019;144:1310–1319.
  • Ihara F, Sakurai D, Yonekura S, et al. Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy. Allergy. 2018;73:1823–1832.
  • Xie S, Fan R, Tang Q, et al. Identification of robust biomarkers for early predicting efficacy of subcutaneous immunotherapy in children with house dust mite-induced allergic rhinitis by multiple cytokine profiling. Front Immunol. 2021;12:805404.
  • Cheng S, Wen S, Xie S, et al. Circulating C-X-C motif ligand 13 as a biomarker for early predicting efficacy of subcutaneous immunotherapy in children with chronic allergic rhinitis. Front Pediatr. 2022;10:872152.
  • Ma TT, Cao MD, Yu RL, et al. Leukotriene A(4) hydrolase is a candidate predictive biomarker for successful allergen immunotherapy. Front Immunol. 2020;11:559746.
  • Guéguen C, Luce S, Lombardi V, et al. IL-10 mRNA levels in whole blood cells correlate with house dust mite allergen immunotherapy efficacy. Allergy. 2019;74:2223–2226.
  • Sakurai D, Yonekura S, Iinuma T, et al. Sublingual immunotherapy for allergic rhinitis: subjective versus objective tools to evaluate its success. Rhinology. 2016;54:221–230.
  • Xie S, Jiang S, Zhang H, et al. Prediction of sublingual immunotherapy efficacy in allergic rhinitis by serum metabolomics analysis. Int Immunopharmacol. 2021;90:107211.
  • Rolland JM, Gardner LM, O’Hehir RE. Functional regulatory T cells and allergen immunotherapy. Curr Opin Allergy Clin Immunol. 2010;10:559–566.
  • Radulovic S, Jacobson MR, Durham SR, et al. Grass pollen immunotherapy induces Foxp3-expressing CD4+ CD25+ cells in the nasal mucosa. J Allergy Clin Immunol. 2008;121:1467–1472.
  • Scadding GW, Shamji MH, Jacobson MR, et al. Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin a and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells. Clin Exp Allergy. 2010;40:598–606.
  • Mauri C, Bosma A. Immune regulatory function of B cells. Annu Rev Immunol. 2012;30:221–241.
  • Stanic B, van de Veen W, Wirz OF, et al. IL-10-overexpressing B cells regulate innate and adaptive immune responses. J Allergy Clin Immunol. 2015;135:771–780.
  • Angelini F, Pacciani V, Corrente S, et al. Dendritic cells modification during sublingual immunotherapy in children with allergic symptoms to house dust mites. World J Pediatr. 2011;7:24–30.
  • Piconi S, Trabattoni D, Rainone V, et al. Immunological effects of sublingual immunotherapy: clinical efficacy is associated with modulation of programmed cell death ligand 1, IL-10, and IgG4. J Immunol. 2010;185:7723–7730.
  • Syed A, Garcia MA, Lyu SC, et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol. 2014;133:500–510.
  • Guideline on the Clinical Development of Products for Specific Immunotherapy for the Treatment of Allergic Diseases [ Cited 2023 Mar 04]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-development-products-specific-immunotherapy-treatment-allergic-diseases_en.pdf.
  • Petsky HL, Kew KM, Chang AB. Exhaled nitric oxide levels to guide treatment for children with asthma. Cochrane Database Syst Rev. 2016;11:Cd011439.
  • Petsky HL, Kew KM, Turner C, et al. Exhaled nitric oxide levels to guide treatment for adults with asthma. Cochrane Database Syst Rev. 2016;9:Cd011440.
  • Gauvreau GM, Davis BE, Scadding G, et al. Allergen provocation tests in respiratory research: building on 50 years of experience. Eur Respir J. 2022;60(2):2102782. DOI:10.1183/13993003.02782-2021
  • 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;124:471–477.
  • Scadding GW, Eifan A, Penagos M, et al. Local and systemic effects of cat allergen nasal provocation. Clin Exp Allergy. 2015;45:613–623.
  • Pfaar O, Calderon MA, Andrews CP, et al. Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future - an EAACI position paper. Allergy. 2017;72:1035–1042.
  • Pfaar O, Zieglmayer P. Allergen exposure chambers: implementation in clinical trials in allergen immunotherapy. Clin Transl Allergy. 2020;10:33.
  • Hossenbaccus L, Steacy LM, Walker T, et al. Utility of environmental exposure unit challenge protocols for the study of allergic rhinitis therapies. Curr Allergy Asthma Rep. 2020;20:34.
  • Jacobs RL, Harper N, He W, et al. Effect of confounding cofactors on responses to pollens during natural season versus pollen challenge chamber exposure. J Allergy Clin Immunol. 2014;133:1340–1346.
  • Ellis AK, Jacobs RL, Tenn MW, et al. Clinical standardization of two controlled allergen challenge facilities: the environmental exposure unit and the biogenics research chamber. Annals of Allergy, Asthma & Immunol. 2019;122:639–46.e2.
  • Larson D, Patel P, Salapatek AM, et al. Nasal allergen challenge and environmental exposure chamber challenge: a randomized trial comparing clinical and biological responses to cat allergen. J Allergy Clin Immunol. 2020;145:1585–1597.
  • Scadding GW, Calderon MA, Bellido V, et al. Optimisation of grass pollen nasal allergen challenge for assessment of clinical and immunological outcomes. J Immunol Methods. 2012;384:25–32.
  • Pfaar O, Demoly P, Gerth van Wijk R, et al. Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI position paper. Allergy. 2014;69:854–867.
  • Sousa-Pinto B, Azevedo LF, Jutel M, et al. Development and validation of combined symptom-medication scores for allergic rhinitis. Allergy. 2022;77:2147–2162.
  • DuBuske LM, Frew AJ, Horak F, et al. Ultrashort-specific immunotherapy successfully treats seasonal allergic rhinoconjunctivitis to grass pollen. Allergy Asthma Proc. 2011;32:239–247.
  • Kirtland ME, Tsitoura DC, Durham SR, et al. Toll-like receptor agonists as adjuvants for allergen immunotherapy. Front Immunol. 2020;11:599083. DOI:10.3389/fimmu.2020.599083
  • Jutel M, Jaeger L, Suck R, et al. Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol. 2005;116:608–613. DOI:10.1016/j.jaci.2005.06.004
  • 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;122:951–960. DOI:10.1016/j.jaci.2008.09.017
  • Corrigan CJ, Kettner J, Doemer C, et al. Efficacy and safety of preseasonal-specific immunotherapy with an aluminium-adsorbed six-grass pollen allergoid. Allergy. 2005;60:801–807. DOI:10.1111/j.1398-9995.2005.00790.x
  • Mösges R, Rohdenburg C, Eichel A, et al. Dose-finding study of carbamylated monomeric allergoid tablets in grass-allergic rhinoconjunctivitis patients. Immunotherapy. 2017;9:1225–1238.
  • Atanasio A, Franklin MC, Kamat V, et al. Targeting immunodominant Bet v 1 epitopes with monoclonal antibodies prevents the birch allergic response. J Allergy Clin Immunol. 2022;149:200–211. DOI:10.1016/j.jaci.2021.05.038
  • Orengo JM, Radin AR, Kamat V, et al. Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement. Nat Commun. 2018;9:1421. DOI:10.1038/s41467-018-03636-8
  • Har D, Lee MJ. Systemic reaction rates with omalizumab, subcutaneous immunotherapy, and combination therapy in children with allergic asthma. Allergy Asthma Proc. 2019;40:35–40.
  • Incorvaia C, Martignago I, Ridolo E. Use of a combination of allergen immunotherapy and omalizumab for prevention of anaphylaxis. Current Treatment Options in Allergy. 2018;5:155–165. DOI:10.1007/s40521-018-0170-8
  • Atipas K, Kanjanawasee D, Tantilipikorn P. Intradermal allergen immunotherapy for allergic rhinitis: current evidence. J Pers Med. 2022;12:12.
  • Slovick A, Douiri A, Muir R, et al. Intradermal grass pollen immunotherapy increases T(H)2 and IgE responses and worsens respiratory allergic symptoms. J Allergy Clin Immunol. 2017;139:1830–9.e13.
  • 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;129:128–135.
  • Senti G, von Moos S, Tay F, et al. Determinants of efficacy and safety in epicutaneous allergen immunotherapy: summary of three clinical trials. Allergy. 2015;70:707–710.
  • Zylke JW. Epicutaneous immunotherapy vs placebo for peanut protein ingestion among peanut-allergic children. JAMA. 2019;321:956.
  • von Moos S, Johansen P, Tay F, et al. Comparing safety of abrasion and tape-stripping as skin preparation in allergen-specific epicutaneous immunotherapy. J Allergy Clin Immunol. 2014;134:965–967.
  • 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.
  • 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;105:17908–17912. DOI:10.1073/pnas.0803725105
  • Slifka MK, Amanna IJ. Chapter: 8 Passive Immunization. In: Plotkin SA, Orenstein WA, Offit PA, Edwards KM editors. Plotkin’s Vaccines. 7th ed. 2018. p. 84–95.e10. DOI;10.1016/B978-0-323-35761-6.00008-0
  • Albrecht M, Arck PC. Vertically transferred immunity in neonates: mothers, mechanisms and mediators. Front Immunol. 2020;11:555.
  • Behring K. On the development of immunity to diphtheria and tetanus in animals. Dtsch Med Wochenschr. 1965;90:2183.
  • Grundbacher FJ. Behring’s discovery of diphtheria and tetanus antitoxins. Immunol Today. 1992;13:188–190.
  • Marcotte H, Hammarström L. Chapter: 71 Passive Immunization: Toward Magic Bullets. In: Mestecky J, Strober W, Russell MW, Kelsall BL, Cheroutre H, Lambrecht BN. editors. Mucosal Immunology. 4th ed. Academic Press; 2015. p. 1403–1434. DOI:10.1016/B978-0-12-415847-4.00071-9
  • Manohar A, Ahuja J, Crane JK. Immunotherapy for infectious diseases: past, present, and future. Immunol Invest. 2015;44:731–737.
  • Prausnitz CH. Küstner: Studien über die Überempfindlichkeit. Centralbl F Bakt(orig). 1921;86:16.
  • Johansson SG, Bennich H. Immunological studies of an atypical (myeloma) immunoglobulin. Immunology. 1967;13:381–394.
  • Ishizaka K, Ishizaka T, Hornbrook MM. Physico-chemical properties of human reaginic antibody. IV. Presence of a unique immunoglobulin as a carrier of reaginic activity. J Immunol. 1966;97:75–85.
  • Cooke RA, Barnard JH, Hebald S, et al. Serological evidence of immunity with coexisting sensitization in a type of human allergy (hay fever). J Exp Med. 1935;62:733–750.
  • Lighaam LC, Rispens T. The immunobiology of immunoglobulin G4. Semin Liver Dis. 2016;36:200–215.
  • Flicker S, Steinberger P, Norderhaug L, et al. Conversion of grass pollen allergen-specific human IgE into a protective IgG(1) antibody. Eur J Immunol. 2002;32:2156–2162.
  • Zinkhan S, Thoms F, Augusto G, et al. On the role of allergen-specific IgG subclasses for blocking human basophil activation. Front Immunol. 2022;13:892631.
  • Flicker S, Valenta R. Renaissance of the blocking antibody concept in type I allergy. Int Arch Allergy Immunol. 2003;132:13–24. DOI:10.1159/000073260
  • James LK. The cloning and expression of human monoclonal antibodies: implications for allergen immunotherapy. Curr Allergy Asthma Rep. 2016;16:15. DOI:10.1007/s11882-015-0588-z
  • Matson AP, Thrall RS, Rafti E, et al. Breastmilk from allergic mothers can protect offspring from allergic airway inflammation. Breastfeed Med. 2009;4:167–174.
  • Lupinek C, Hochwallner H, Johansson C, et al. Maternal allergen-specific IgG might protect the child against allergic sensitization. J Allergy Clin Immunol. 2019;144:536–548.
  • Flicker S, Linhart B, Wild C, et al. Passive immunization with allergen-specific IgG antibodies for treatment and prevention of allergy. Immunobiology. 2013;218:884–891.
  • Storni F, Cabral-Miranda G, Roesti E, et al. A single monoclonal antibody against the peanut allergen Ara h 2 protects against systemic and local peanut allergy. Int Arch Allergy Immunol. 2020;181:334–341.
  • Paolucci M, Wuillemin N, Homère V, et al. Targeting Ara h 2 with human-derived monoclonal antibodies prevents peanut-induced anaphylaxis in mice. Allergy. 2023. DOI:10.1111/all.15659
  • Shamji MH, Singh I, Layhadi JA, et al. Passive prophylactic administration with a single dose of anti-fel d 1 monoclonal antibodies REGN1908-1909 in cat allergen-induced allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial. Am J Respir Crit Care Med. 2021;204:23–33. DOI:10.1164/rccm.202011-4107OC
  • Gevaert P, De Craemer J, De Ruyck N, et al. Novel antibody cocktail targeting Bet v 1 rapidly and sustainably treats birch allergy symptoms in a phase 1 study. J Allergy Clin Immunol. 2022;149:189–199. DOI:10.1016/j.jaci.2021.05.039
  • Flicker S, Gadermaier E, Madritsch C, et al. Passive immunization with allergen-specific antibodies. Curr Top Microbiol Immunol. 2011;352:141–159.
  • Wickman M. When allergies complicate allergies. Allergy. 2005;60(79):14–18.
  • Satyaraj E, Wedner HJ, Bousquet J. Keep the cat, change the care pathway: a transformational approach to managing Fel d 1, the major cat allergen. Allergy. 2019;74(107):5–17.
  • Strait RT. IgG-blocking antibodies inhibit IgE-mediated anaphylaxis in vivo through both antigen interception and Fc RIIb cross-linking. J Clin Invest. 2006;116:833–841.
  • Eckl-Dorna J, Villazala-Merino S, Linhart B, et al. Allergen-specific antibodies regulate secondary allergen-specific immune responses. Front Immunol. 2018;9:3131.
  • Wachholz PA, Soni NK, Till SJ, et al. Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J Allergy Clin Immunol. 2003;112:915–922.
  • Keizer RJ, Huitema AD, Schellens JH, et al. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010;49:493–507.
  • Kamal MA, Dingman R, Wang CQ, et al. REGN1908-1909 monoclonal antibodies block Fel d 1 in cat allergic subjects: translational pharmacokinetics and pharmacodynamics. Clin Transl Sci. 2021;14:2440–2449.
  • Baldo BA. Immune- and non-immune-mediated adverse effects of monoclonal antibody therapy: a survey of 110 approved antibodies. Antibodies (Basel). 2022;11:17.
  • Bernstein IL, Michael JG, Malkiel S, et al. Immunoregulatory function of specific IgG. II. Clinical evaluation of combined active and passive immunotherapy. Int Arch Allergy Appl Immunol. 1979;58:30–37.
  • Bousquet J, Fontez A, Aznar R, et al. Combination of passive and active immunization in honeybee venom immunotherapy. J Allergy Clin Immunol. 1987;79:947–954.
  • Müller UR, Morris T, Bischof M, et al. Combined active and passive immunotherapy in honeybee-sting allergy. J Allergy Clin Immunol. 1986;78:115–122.
  • Casale TB, Busse WW, Kline JN, et al. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2006;117:134–140.
  • Massanari M, Nelson H, Casale T, et al. Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma. J Allergy Clin Immunol. 2010;125:383–389.
  • Kuehr J, Brauburger J, Zielen S, et al. Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis. J Allergy Clin Immunol. 2002;109:274–280.
  • Kopp MV, Hamelmann E, Zielen S, et al. Combination of omalizumab and specific immunotherapy is superior to immunotherapy in patients with seasonal allergic rhinoconjunctivitis and co-morbid seasonal allergic asthma. Clin Exp Allergy. 2009;39:271–279.
  • Rolinck-Werninghaus C, Hamelmann E, Keil T, et al. The co-seasonal application of anti-IgE after preseasonal specific immunotherapy decreases ocular and nasal symptom scores and rescue medication use in grass pollen allergic children. Allergy. 2004;59:973–979.
  • Pajno GB, Fernandez-Rivas M, Arasi S, et al. EAACI guidelines on allergen immunotherapy: IgE-mediated food allergy. Allergy. 2018;73:799–815.
  • Passanisi S, Caminiti L, Zirilli G, et al. Biologics in food allergy: up-to-date. Expert Opin Biol Ther. 2021;21:1227–1235. DOI:10.1080/14712598.2021.1904888
  • Reinwald S, Rolland JM, O’Hehir RE, et al. Peanut oral immunotherapy: current trends in clinical trials. Immunother Adv. 2022;2:4. DOI:10.1093/immadv/ltac004
  • Langlois A, Lavergne MH, Leroux H, et al. Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy. Allergy, Asthma Clin Immunol. 2020;16:25.
  • Brandström J, Vetander M, Sundqvist AC, et al. Individually dosed omalizumab facilitates peanut oral immunotherapy in peanut allergic adolescents. Clin Exp Allergy. 2019;49:1328–1341.
  • Omalizumab as monotherapy and as adjunct therapy to multi-allergen OIT in food allergic participants (OUtMATCH). Identifier: nCT03881696. [cited 2023 Mar 4]. [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT03881696:
  • Wood RA, Kim JS, Lindblad R, et al. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow’s milk allergy. J Allergy Clin Immunol. 2016;137:1103–1110.
  • Dupilumab as an adjunct for subcutaneous grass immunotherapy. Identifier NCT03558997. [cited 2023 Mar 4]. [Internet]. Available from: https://ClinicalTrials.gov/show/NCT03558997
  • Grass Pollen Immunotherapy Plus Dupilumab for Tolerance Induction. Identifier NCT04502966. [Internet]. [ cited 2023 Mar 04]. Available from: https://ClinicalTrials.gov/show/NCT04502966
  • Study in pediatric subjects with peanut allergy to evaluate efficacy and safety of dupilumab as adjunct to AR101 (Peanut oral immunotherapy). Identifier NCT03682770. [ cited 2023 Mar 04]. [Internet]. Available from: https://ClinicalTrials.gov/show/NCT03682770
  • Clinical study using biologics to improve multi OIT outcomes. Identifier NCT03679676. [ cited 2023 Mar 04] [Internet]. Available from: https://ClinicalTrials.gov/show/NCT03679676
  • Dupilumab and milk OIT for the treatment of cow’s milk allergy. Identifier NCT04148352. [cited 2023 Mar 04] [Internet]. Available from: https://ClinicalTrials.gov/show/NCT04148352
  • Burbank AJ, Sood P, Vickery BP, et al. Oral immunotherapy for food allergy. Immunol Allergy Clin North Am. 2016;36:55–69.
  • Sampath V, Sindher SB, Alvarez Pinzon AM, et al. Can food allergy be cured? What are the future prospects? Allergy. 2020;75:1316–1326.
  • MHK H, Wong WHS, Heine RG, et al. Early clinical predictors of remission of peanut allergy in children. J Allergy Clin Immunol. 2008;121:731–736.
  • Pouessel G, Lezmi G. Oral immunotherapy for food allergy: translation from studies to clinical practice? World Allergy Organ J. 2023;16:100747.
  • Grabenhenrich LB, Dölle S, Moneret-Vautrin A, et al. Anaphylaxis in children and adolescents: the European anaphylaxis registry. J Allergy Clin Immunol. 2016;137:1128–37.e1.
  • Herbert L, Marchisotto MJ, Vickery B. Patients’ perspectives and needs on novel food allergy treatments in the United States. Curr Treat Options Allergy. 2021;8:9–20.
  • Fernandez-Rivas M, Vereda A, Vickery BP, et al. Open-label follow-on study evaluating the efficacy, safety, and quality of life with extended daily oral immunotherapy in children with peanut allergy. Allergy. 2022;77:991–1003.
  • Bajzik V, DeBerg HA, Garabatos N, et al. Oral desensitization therapy for peanut allergy induces dynamic changes in peanut-specific immune responses. Allergy. 2022;77:2534–2548.
  • Wambre E, Bajzik V, DeLong JH, et al. A phenotypically and functionally distinct human T(H)2 cell subpopulation is associated with allergic disorders. Sci Transl Med. 2017;9. DOI:10.1126/scitranslmed.aam9171
  • Vickery BP, Scurlock AM, Kulis M, et al. Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol. 2014;133:468–475.
  • Lazizi S, Labrosse R, Graham F. Transitioning peanut oral immunotherapy to clinical practice. Front Allergy. 2022;3:974250.
  • Yu W, Freeland DMH, Nadeau KC. Food allergy: immune mechanisms, diagnosis and immunotherapy. Nat Rev Immunol. 2016;16:751–765. DOI:10.1038/nri.2016.111
  • Jones SM, Kim EH, Nadeau KC, et al. Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the immune tolerance network IMPACT trial): a randomised placebo-controlled study. Lancet. 2022;399:359–371.
  • Elizur A, Appel MY, Nachshon L, et al. Walnut oral immunotherapy for desensitisation of walnut and additional tree nut allergies (Nut CRACKER): a single-centre, prospective cohort study. Lancet Child & Adolescent Health. 2019;3:312–321.
  • Elizur A, Appel MY, Nachshon L, et al. Cashew oral immunotherapy for desensitizing cashew-pistachio allergy (NUT CRACKER study). Allergy. 2022;77:1863–1872.
  • Nowak-Węgrzyn A, Wood RA, Nadeau KC, et al. Multicenter, randomized, double-blind, placebo-controlled clinical trial of vital wheat gluten oral immunotherapy. J Allergy Clin Immunol. 2019;143:651–661.
  • Palosuo K, Karisola P, Savinko T, et al. A randomized, open-label trial of hen’s egg oral immunotherapy: efficacy and humoral immune responses in 50 children. J Allergy Clin Immunol Pract. 2021;9:1892–1901.
  • Maeda M, Imai T, Ishikawa R, et al. Effect of oral immunotherapy in children with milk allergy: the ORIMA study. Allergol Int. 2021;70:223–228.
  • Epstein-Rigbi N, Levy MB, Nachshon L, et al. Efficacy and safety of food allergy oral immunotherapy in adults. Allergy. 2022;78:803–811.
  • Wang J. Management of the patient with multiple food allergies. Curr Allergy Asthma Rep. 2010;10:271–277.
  • Gasich L, Fergeson J, Ly J. Multi-food oral immunotherapy as safe and effective as single food therapy. J Allergy Clin Immunol. 2020;145:AB133.
  • Bégin P, Winterroth LC, Dominguez T, et al. Safety and feasibility of oral immunotherapy to multiple allergens for food allergy. Allergy, Asthma & Clin Immunol. 2014;10:1.
  • Taudorf E, Weeke B. Orally administered grass pollen. Allergy. 1983;38:561–564.
  • Durham SR, Shamji MH. Allergen immunotherapy: past, present and future. Nat Rev Immunol. 2022;1–12. DOI:10.1038/s41577-022-00786-1
  • Perkin MR. Palforzia for peanut allergy: panacea or predicament. Clin Exp Allergy. 2022;52:729–731.
  • Mustafa SS, Patrawala S. Real world adoption of FDA-approved peanut oral immunotherapy with palforzia. J Allergy Clin Immunol. 2021;147:108.
  • Senti G, Johansen P, Kündig TM. Intralymphatic immunotherapy. Curr Opin Allergy Clin Immunol. 2009;9:537–543.
  • Hoang MP, Seresirikachorn K, Chitsuthipakorn W, et al. Intralymphatic immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta-analysis. Rhinology. 2021;59:236–244.
  • Werner MT, Bosso JV. Intralymphatic immunotherapy for allergic rhinitis: a systematic review and meta-analysis. Allergy Asthma Proc. 2021;42:283–292.
  • Hoffmann HJ, Hviid-Vyff B. Strengthening the case for intralymphatic immunotherapy. Curr Opin Allergy Clin Immunol. 2022;22:387–395.
  • Konradsen JR, Grundstrom J, Hellkvist L, et al. Intralymphatic immunotherapy in pollen-allergic young adults with rhinoconjunctivitis and mild asthma: a randomized trial. J Allergy Clin Immunol. 2020;145:1005–7 e7.
  • Hellkvist L, Hjalmarsson E, Weinfeld D, et al. High dose pollen intralymphatic immunotherapy: two RDBPC trials question the benefit of dose increase. Allergy. 2021;77(3): 883–896. DOI:10.1111/all.15042
  • Hellkvist L, Hjalmarsson E, Kumlien Georen S, et al. Intralymphatic immunotherapy with 2 concomitant allergens, birch and grass: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2018;142:1338–41 e9.
  • Hylander T, Latif L, Petersson-Westin U, et al. Intralymphatic allergen-specific immunotherapy: an effective and safe alternative treatment route for pollen-induced allergic rhinitis. J Allergy Clin Immunol. 2013;131:412–420.
  • Hylander T, Larsson O, Petersson-Westin U, et al. Intralymphatic immunotherapy of pollen-induced rhinoconjunctivitis: a double-blind placebo-controlled trial. Respir Res. 2016;17:10.
  • Witten M, Malling HJ, Blom L, et al. Is intralymphatic immunotherapy ready for clinical use in patients with grass pollen allergy? J Allergy Clin Immunol. 2013;132:1248–1252.
  • Weinfeld D, Westin U, Hellkvist L, et al. A preseason booster prolongs the increase of allergen specific IgG4 levels, after basic allergen intralymphatic immunotherapy, against grass pollen seasonal allergy. Allergy, Asthma Clin Immunol. 2020;16:31.
  • Thompson CP, Silvers S, Shapiro MA. Intralymphatic immunotherapy for mountain cedar pollinosis: a randomized, double-blind, placebo-controlled trial. Annals of Allergy, Asthma & Immunol. 2020;125:311–318.
  • Skaarup SH, Schmid JM, Skjold T, et al. Intralymphatic immunotherapy improves grass pollen allergic rhinoconjunctivitis: a 3-year randomized placebo-controlled trial. J Allergy Clin Immunol. 2021;147:1011–1019.
  • Skaarup SH, Graumann O, Schmid J, et al. The number of successful injections associates with improved clinical effect in intralymphatic immunotherapy. Allergy. 2021;76:1859–1861.
  • Ahlbeck L, Ahlberg E, Nystrom U, et al. Intralymphatic allergen immunotherapy against pollen allergy: a 3-year open follow-up study of 10 patients. Annals of Allergy, Asthma & Immunol. 2018;121:626–627.
  • Ahlbeck L, Ahlberg E, Björkander J, et al. Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen. Clin Exp Allergy. 2022;52:747–759.
  • Ahlbeck L, Ahlberg E, Stuivers L, et al. Intralymphatic immunotherapy with birch and grass pollen extracts. A randomized double-blind placebo-controlled clinical trial. Clin Exp Allergy. 2023. DOI:10.1111/cea.14307.
  • Kundig TM, Johansen P, Bachmann MF, et al. Intralymphatic immunotherapy: time interval between injections is essential. J Allergy Clin Immunol. 2014;133:930–931.
  • Hjálmsdóttir Á, Wäckerle-Men Y, Duda A, et al. Dosing intervals in intralymphatic immunotherapy. Clin Exp Allergy. 2016;46:504–507.
  • Aini NR, Mohd Noor N, Md Daud MK, et al. Efficacy and safety of intralymphatic immunotherapy in allergic rhinitis: a systematic review and meta-analysis. Clin Transl Allergy. 2021;11:e12055.
  • Martínez-Gómez JM, Johansen P, Erdmann I, et al. Intralymphatic injections as a new administration route for allergen-specific immunotherapy. Int Arch Allergy Immunol. 2009;150:59–65.
  • Smith KA, Tam VL, Wong RM, et al. Enhancing DNA vaccination by sequential injection of lymph nodes with plasmid vectors and peptides. Vaccine. 2009;27:2603–2615.
  • Šl AY, Senti G, Lang CCV, et al. Quality of life in allergic rhinitis patients treated with intralymphatic immunotherapy (ILIT): a 19-year follow-up. J Allergy Clin Immunol: Global. 2023;2:43–50.
  • Hjalmarsson E, Hellkvist L, Karlsson A, et al. A five-year open follow up of a randomized, double-blind placebo-controlled trial of intralymphatic immunotherapy for birch and grass reveals remaining beneficial effects. J Investig Allergol Clin Immunol. 2022;33:0.
  • Hellkvist L, Hjalmarsson E, Weinfeld D, et al. High-dose pollen intralymphatic immunotherapy: two RDBPC trials question the benefit of dose increase. Allergy. 2022;77:883–896.
  • Senti G, Crameri R, Kuster D, et al. Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections. J Allergy Clin Immunol. 2012;129:1290–1296.
  • Zaleska A, Eiwegger T, Soyer O, et al. Immune regulation by intralymphatic immunotherapy with modular allergen translocation MAT vaccine. Allergy. 2014;69:1162–1170.
  • Freiberger SN, Zehnder M, Gafvelin G, et al. IgG4 but no IgG1 antibody production after intralymphatic immunotherapy with recombinant MAT-Feld1 in human. Allergy. 2016;71:1366–1370.
  • Chabot A, Senti G, Erdmann I, et al. Intralymphatic Immunotherapy (ILIT) with bee venom allergens: a clinical proof-of-concept study and the very first ILIT in humans. Front Allergy. 2022;3:832010.
  • Compalati E, Incorvaia C, Cavaliere C, et al. The role of allergoids in allergen immunotherapy: from injective to sublingual route. Eur Ann Allergy Clin Immunol. 2020;52:195–204.
  • Jensen-Jarolim E, Bachmann MF, Bonini S, et al. State-of-the-art in marketed adjuvants and formulations in allergen immunotherapy: a position paper of the European Academy of Allergy and Clinical Immunology (EAACI). Allergy. 2020;75:746–760.
  • Del Río P R, Vidal C, Just J, et al. The European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): a paediatric assessment. Pediatr Allergy Immunol. 2017;28:60–70.
  • Patel P, Salapatek AM. Pollinex Quattro: a novel and well-tolerated, ultra short-course allergy vaccine. Expert Rev Vaccines. 2006;5:617–629.
  • Rosewich M, Lee D, Zielen S. Pollinex Quattro: an innovative four injections immunotherapy in allergic rhinitis. Hum Vaccin Immunother. 2013;9:1523–1531.
  • Zhao X, Wu H, Lin L, et al. Effect and safety analysis of allergovit standardized mite allergen immunotherapy in patients with allergic rhinitis. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2013;27:1128–1131.
  • Grzeskowiak LE, Tao B, Aliakbari K, et al. Oral immunotherapy using boiled peanuts for treating peanut allergy: an open-label, single-arm trial. Clin Exp Allergy. 2023;53:327–336.
  • Johansen P, Senti G, Martínez Gómez JM, et al. Heat denaturation, a simple method to improve the immunotherapeutic potential of allergens. Eur J Immunol. 2005;35:3591–3598.
  • Jensen-Jarolim E, Roth-Walter F, Jordakieva G, et al. Allergens and adjuvants in allergen immunotherapy for immune activation, tolerance, and resilience. J Allergy Clin Immunol Pract. 2021;9:1780–1789.
  • Kopp MV, Bovermann X, Klimek L. Accelerated dose escalation with three injections of an aluminum hydroxide-adsorbed allergoid preparation of six grasses is safe for patients with moderate to severe allergic rhinitis. Int Arch Allergy Immunol. 2020;181:94–102.
  • Chaker AM, Al-Kadah B, Luther U, et al. An accelerated dose escalation with a grass pollen allergoid is safe and well-tolerated: a randomized open label phase II trial. Clin Transl Allergy. 2015;6:4.
  • Zielen S, Plückhahn K, Akboga Y, et al. Fast up-dosing with a birch allergoid is safe and well tolerated in allergic rhinitis patients with or without asthma. Immunotherapy. 2019;11:177–187.
  • Pfaar O, van Twuijver E, Hecker H, et al. Accelerated up-dosing of subcutaneous immunotherapy with a registered allergoid grass pollen preparation. Int Arch Allergy Immunol. 2013;160:420–424.
  • Mahler V, Zielen S, Rosewich M. Year-round treatment initiation for a 6-grasses pollen allergoid in specific immunotherapy of allergic rhinoconjunctivitis and asthma. Immunotherapy. 2019;11:1569–1582.
  • Pfaar O, Hohlfeld JM, Al-Kadah B, et al. Dose-response relationship of a new Timothy grass pollen allergoid in comparison with a 6-grass pollen allergoid. Clin Exp Allergy. 2017;47:1445–1455.
  • Becker S, Zieglmayer P, Canto G, et al. A meta-analysis on allergen-specific immunotherapy using MCT(®) (MicroCrystalline Tyrosine)-adsorbed allergoids in pollen allergic patients suffering from allergic rhinoconjunctivitis. Clin Transl Allergy. 2021;11:e12037.
  • Pfaar O, Nell MJ, Boot JD, et al. A randomized, 5-arm dose finding study with a mite allergoid SCIT in allergic rhinoconjunctivitis patients. Allergy. 2016;71:967–976.
  • Jutel M, Rudert M, Kreimendahl F, et al. Efficacy and tolerability of a house dust mite allergoid in allergic bronchial asthma: a randomized dose-ranging trial. Immunotherapy. 2018;10:1149–1161.
  • Durham SR. Sustained effects of grass pollen AIT. Allergy. 2011;66(95):50–52.
  • Durham SR, Emminger W, Kapp A, et al. Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. J Allergy Clin Immunol. 2010;125:131–138.
  • Sidenius K, Arvidsson P, Indbryn R, et al. A real-life one-year non-interventional study assessing safety, tolerability, and treatment outcome of the SQ HDM SLIT-Tablet (Acarizax(®)) in house dust mite allergic rhinitis with or without asthma. Pulm Ther. 2021;7:221–236.
  • Dorofeeva Y, Shilovskiy I, Tulaeva I, et al. Past, present, and future of allergen immunotherapy vaccines. Allergy. 2021;76:131–149.
  • Linhart B, Valenta R. Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives. Vaccine. 2012;30:4328–4335.
  • Wraith DC, Krishna MT. Peptide allergen-specific immunotherapy for allergic airway diseases-state of the art. Clin Exp Allergy. 2021;51:751–769.
  • Anderton SM, Viner NJ, Matharu P, et al. Influence of a dominant cryptic epitope on autoimmune T cell tolerance. Nat Immunol. 2002;3:175–181.
  • Burton BR, Britton GJ, Fang H, et al. Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy. Nat Commun. 2014;5:4741.
  • Kettner A, DellaCorte G, de Blay F, et al. Benefit of Bet v 1 contiguous overlapping peptide immunotherapy persists during first follow-up season. J Allergy Clin Immunol. 2018;142:678–80.e7.
  • Spertini F, DellaCorte G, Kettner A, et al. Efficacy of 2 months of allergen-specific immunotherapy with Bet v 1-derived contiguous overlapping peptides in patients with allergic rhinoconjunctivitis: results of a phase IIb study. J Allergy Clin Immunol. 2016;138:162–168.
  • Ellis AK, Frankish CW, O’Hehir RE, et al. Treatment with grass allergen peptides improves symptoms of grass pollen-induced allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2017;140:486–496.
  • Shamji MH, Ceuppens J, Bachert C, et al. Lolium perenne peptides for treatment of grass pollen allergy: a randomized, double-blind, placebo-controlled clinical trial. J Allergy Clin Immunol. 2018;141:448–451.
  • Mösges R, Bachert C, Panzner P, et al. Short course of grass allergen peptides immunotherapy over 3 weeks reduces seasonal symptoms in allergic rhinoconjunctivitis with/without asthma: a randomized, multicenter, double-blind, placebo-controlled trial. Allergy. 2018;73:1842–1850.
  • 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.
  • 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;167:1734–1739.
  • Ellis AK, Frankish CW, Armstrong K, et al. Persistence of the clinical effect of grass allergen peptide immunotherapy after the second and third grass pollen seasons. J Allergy Clin Immunol. 2020;145:610–8.e9.
  • 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. 2013;131:103–109.
  • 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.
  • Maguire P, Nicodemus C, Robinson D, et al. The safety and efficacy of ALLERVAX CAT in cat allergic patients. Clin Immunol. 1999;93:222–231.
  • Linhart B, Narayanan M, Focke-Tejkl M, et al. Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides lacking allergen-specific T cell epitopes reduces Bet v 1-specific T cell responses via blocking antibodies in a murine model for birch pollen allergy. Clin Exp Allergy. 2014;44:278–287.
  • Incorvaia C, Al-Ahmad M, Ansotegui IJ, et al. Personalized medicine for allergy treatment: allergen immunotherapy still a unique and unmatched model. Allergy. 2021;76:1041–1052.
  • Jacquet A. Nucleic acid vaccines and CpG oligodeoxynucleotides for allergen immunotherapy. Curr Opin Allergy Clin Immunol. 2021;21:569–575.
  • Su Y, Romeu-Bonilla E, Anagnostou A, et al. Safety and long-term immunological effects of CryJ2-LAMP plasmid vaccine in Japanese red cedar atopic subjects: a phase I study. Hum Vaccin Immunother. 2017;13:2804–2813.
  • Akinfenwa O, Rodríguez-Domínguez A, Vrtala S, et al. Novel vaccines for allergen-specific immunotherapy. Curr Opin Allergy Clin Immunol. 2021;21:86–99.
  • Pfaar O, Bachert C, Bufe A, et al. Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases: s2k guideline of the German society for allergology and clinical immunology (DGAKI), the society for pediatric allergy and environmental medicine (GPA), the Medical Association of German allergologists (AeDA), the Austrian Society for Allergy and Immunology (OGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto- Rhino-Laryngology, head and neck surgery (DGHNO-KHC), the German Society of Pediatrics and adolescent medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German association of ENT surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal association of pulmonologists (BDP) and the German dermatologists association (BVDD). Allergo J Int. 2014;23:282–319.
  • Holt PG, Sly PD, Sampson HA, et al. Prophylactic use of sublingual allergen immunotherapy in high-risk children: a pilot study. J Allergy Clin Immunol. 2013;132:991–3.e1.
  • Ponce M, Schroeder F, Bannert C, et al. Preventive sublingual immunotherapy with house dust mite extract modulates epitope diversity in pre-school children. Allergy. 2019;74:780–787.
  • Gradman J, Halken S. Preventive effect of allergen immunotherapy on asthma and new sensitizations. J Allergy Clin Immunol Pract. 2021;9:1813–1817.
  • Weiss R, Scheiblhofer S, Roesler E, et al. Prophylactic mRNA vaccination against allergy. Curr Opin Allergy Clin Immunol. 2010;10:567–574.
  • Crespo JF, Cabanillas B. Recent advances in cellular and molecular mechanisms of IgE-mediated food allergy. Food Chem. 2023;411:135500.
  • Du Toit G, Roberts G, Sayre PH, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803–813.
  • Flicker S, Marth K, Kofler H, et al. Placental transfer of allergen-specific IgG but not IgE from a specific immunotherapy–treated mother. J Allergy Clin Immunol. 2009;124:1358–60.e1.
  • Wilcock LK, Francis JN, Durham SR. Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated human peripheral blood mononuclear cells. Clin Exp Allergy. 2004;34:1373–1378.
  • Durham SR, Ying S, Varney VA, et al. Grass pollen immunotherapy inhibits allergen-induced infiltration of CD4+ T lymphocytes and eosinophils in the nasal mucosa and increases the number of cells expressing messenger RNA for interferon-gamma. J Allergy Clin Immunol. 1996;97:1356–1365.
  • Gunawardana NC, Durham SR. New approaches to allergen immunotherapy. Annals of Allergy, Asthma & Immunol. 2018;121:293–305.
  • Klimek L, Schmidt-Weber CB, Kramer MF, et al. Clinical use of adjuvants in allergen-immunotherapy. Expert Rev Clin Immunol. 2017;13:599–610.
  • Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine. 2008;42:145–151.
  • Sun L, Liu W, Zhang LJ. The role of toll-like receptors in skin host defense, psoriasis, and atopic dermatitis. J Immunol Res. 2019;2019:1824624.
  • 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;39:562–570.
  • Klimek L, Willers J, Hammann-Haenni A, et al. Assessment of clinical efficacy of CYT003-QbG10 in patients with allergic rhinoconjunctivitis: a phase IIb study. Clin Exp Allergy. 2011;41:1305–1312.
  • Pohlit H, Bellinghausen I, Frey H, et al. Recent advances in the use of nanoparticles for allergen-specific immunotherapy. Allergy. 2017;72:1461–1474.
  • Basomba A, Tabar AI, de Rojas DH, et al. Allergen vaccination with a liposome-encapsulated extract of dermatophagoides pteronyssinus: a randomized, double-blind, placebo-controlled trial in asthmatic patients. J Allergy Clin Immunol. 2002;109:943–948.
  • Igartua M, Hernández RM, Gutierro I, et al. Preliminary assessment of the immune response to Olea Europaea pollen extracts encapsulated into PLGA microspheres. Pharm Dev Technol. 2001;6:621–627.
  • Marazuela EG, Prado N, Moro E, et al. Intranasal vaccination with poly(lactide-co-glycolide) microparticles containing a peptide T of Ole e 1 prevents mice against sensitization. Clin Exp Allergy. 2008;38:520–528.
  • Pecquet S, Leo E, Fritsché R, et al. Oral tolerance elicited in mice by beta-lactoglobulin entrapped in biodegradable microspheres. Vaccine. 2000;18:1196–1202.
  • Joshi VB, Adamcakova-Dodd A, Jing X, et al. Development of a poly (lactic-co-glycolic acid) particle vaccine to protect against house dust mite induced allergy. Aaps J. 2014;16:975–985.
  • Zhang XQ, Dahle CE, Baman NK, et al. Potent antigen-specific immune responses stimulated by codelivery of CpG ODN and antigens in degradable microparticles. J Immunother. 2007;30:469–478.
  • Chew JL, Wolfowicz CB, Mao HQ, et al. Chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen, Der p 1 for oral vaccination in mice. Vaccine. 2003;21:2720–2729.
  • Phase I trial to evaluate VLP peanut in healthy and peanut allergic subjects (PROTECT). Identifier: nCT05476497. [Internet]. Available from: https://clinicaltrials.gov/ct2/show/NCT05476497: [ cited 04 March 2023].
  • Jensen-Jarolim E. Aluminium in allergies and allergen immunotherapy. World Allergy Organ J. 2015;8:7.
  • Zubeldia JM, Ferrer M, Dávila I, et al. Adjuvants in allergen-specific immunotherapy: modulating and enhancing the immune response. J Investig Allergol Clin Immunol. 2019;29:103–111.
  • Mahler V, Esch RE, Kleine-Tebbe J, et al. Understanding differences in allergen immunotherapy products and practices in North America and Europe. J Allergy Clin Immunol. 2019;143:813–828.
  • Moingeon P. Adjuvants for allergy vaccines. Hum Vaccin Immunother. 2012;8:1492–1498.
  • Lee W, Suresh M. Vaccine adjuvants to engage the cross-presentation pathway. Front Immunol. 2022;13:940047.
  • Hornung V, Bauernfeind F, Halle A, et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008;9:847–856.
  • Ho NI, Huis I‘, Veld LGM, et al. Adjuvants enhancing cross-presentation by dendritic cells: the key to more effective vaccines? Front Immunol. 2018;9:2874.
  • Leuthard DS, Duda A, Freiberger SN, et al. Microcrystalline tyrosine and aluminum as adjuvants in allergen-specific immunotherapy protect from ige-mediated reactivity in mouse models and act independently of inflammasome and TLR signaling. J Immunol. 2018;200:3151–3159.
  • Fonseca DE, Kline JN. Use of CpG oligonucleotides in treatment of asthma and allergic disease. Adv Drug Deliv Rev. 2009;61:256–262.
  • Kline JN, Waldschmidt TJ, Businga TR, et al. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J Immunol. 1998;160:2555–2559.
  • Rodriguez MJ, Mascaraque A, Ramos-Soriano J, et al. Pru p 3-epitope-based sublingual immunotherapy in a murine model for the treatment of peach allergy. Mol Nutr Food Res. 2017;(10):61. DOI:10.1002/mnfr.201700110
  • Montamat G, Leonard C, Poli A, et al. CpG adjuvant in allergen-specific immunotherapy: finding the sweet spot for the induction of immune tolerance. Front Immunol. 2021;12:590054.
  • Garg A, Dewangan HK. Nanoparticles as adjuvants in vaccine delivery. Crit Rev Ther Drug Carrier Syst. 2020;37:183–204.
  • De Souza Rebouças J, Esparza I, Ferrer M, et al. Nanoparticulate adjuvants and delivery systems for allergen immunotherapy. J Biomed Biotechnol. 2012;2012:474605.
  • Martínez Gómez JM, Fischer S, Csaba N, et al. A protective allergy vaccine based on CpG- and protamine-containing PLGA microparticles. Pharm Res. 2007;24:1927–1935.
  • Tasaniyananda N, Chaisri U, Tungtrongchitr A, et al. Mouse model of cat allergic rhinitis and intranasal liposome-adjuvanted refined Fel d 1 vaccine. PLoS ONE. 2016;11:e0150463.
  • Arora N, Gangal SV. Immunomodulation by liposome entrapped allergen. Mol Cell Biochem. 1990;97:173–179.
  • Arora N, Gangal SV. Efficacy of liposome entrapped allergen in down regulation of IgE response in mice. Clin Exp Allergy. 1992;22:35–42.
  • Nigam S, Ghosh PC, Sarma PU. Altered immune response to liposomal allergens of aspergillus fumigatus in mice. Int J Pharm. 2002;236:97–109.
  • Hufnagl K, Afify SM, Braun N, et al. Retinoic acid-loading of the major birch pollen allergen Bet v 1 may improve specific allergen immunotherapy: in silico, in vitro and in vivo data in BALB/c mice. Allergy. 2020;75:2073–2077.
  • Roth-Walter F, Afify SM, Pacios LF, et al. Cow’s milk protein β-lactoglobulin confers resilience against allergy by targeting complexed iron into immune cells. J Allergy Clin Immunol. 2021;147:321–334.
  • Baris S, Kiykim A, Ozen A, et al. Vitamin D as an adjunct to subcutaneous allergen immunotherapy in asthmatic children sensitized to house dust mite. Allergy. 2014;69:246–253.
  • Jerzynska J, Stelmach W, Rychlik B, et al. The clinical effect of vitamin D supplementation combined with grass-specific sublingual immunotherapy in children with allergic rhinitis. Allergy Asthma Proc. 2016;37:105–114.

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