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Review

Investigational new drugs for allergic rhinitis

, , &
Pages 279-292 | Received 15 Oct 2016, Accepted 30 Jan 2017, Published online: 16 Feb 2017

References

  • Casale TB, Stokes JR. Future forms of immunotherapy. J Allergy Clin Immunol. 2011;127:815.
  • Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63:8–160.
  • Noon L. Prophylactic inoculation against hay fever. Lancet. 1911;1:1572.
  • Freeman J. Further observations on the treatment of hay fever by hypodermic inoculations of pollen vaccine. Lancet. 1911;2:814–817.
  • Casale TB, Stokes JR. Immunotherapy: what lies beyond. J Allergy Clin Immunol. 2014;133:612–619.
  • Cox L, Jacobson L. Comparison of allergen immunotherapy practice patterns in the United States and Europe. Ann Allergy Asthma Immunol. 2009;103:451-459; quiz 459-461:495.
  • Focke M, Swoboda I, Marth K, et al. Developments in allergen-specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen-specific immunoglobulin E and T cell reactivity. Clin Exp Allergy. 2010;40:385–397.
  • Calderon MA, Alves B, Jacobson M, et al. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev. 2007;24(1):CD001936.
  • Adkis M, Adkis CA. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors in immune tolerance in allergens. J Allergy Clin Immunol. 2014;133:621–631.
  • Burks AW, Calderon MA, Casale TB, et al. Update on allergy immunotherapy: american Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol. 2013;131:1288–1296.
  • Stokes JR, Casale TB. Allergic rhinitis and asthma: celebrating 100 years of immunotherapy. Curr Opin Immunol. 2011;23(6):808–813.
  • Segal M, Stokes JR, Casale TB. Anti-Immunoglobulin E therapy. World Allergy Organ J. 2008;1:174–183.
  • Casale TB, Busse WW, Kline JN, et al. Immune Tolerance Network Group. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2006;117:134–140.
  • Kopp MV, Hamelmann E, Bendiks M, et al. Transient impact of omalizumab in pollen allergic patients undergoing specific immunotherapy. Pediatr Allergy Immunol. 2013;24:427–433.
  • 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.
  • Li JT, Bernstein DI, Calderon MA, et al. Sublingual grass and ragweed immunotherapy: clinical considerations – a PRACTALL consensus report. J Allergy Clin Immunol. 2016;137:369–376.
  • Creticos PS, Esch RE, Couroux P, et al. Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2014;133:751–758.
  • Durham SR, Yang WH, Pedersen MR, et al. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2006;117:802–809.
  • Didier A, Malling HJ, Worm M, et al. Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol. 2007;120:1338–1345.
  • Lee S, Nolte H, Benninger MS. Clinical considerations in the use of sublingual immunotherapy for allergic rhinitis. Am J Rhinol Allergy. 2015;29:106–114.
  • Canonica GW, Bousquet J, Casale T, et al. Sub-lingual immunotherapy: world allergy organization position paper. World Allergy Org J. 2009;2:233–281.
  • Moingeon P, Mascarell L. Induction of tolerance via the sublingual route: mechanisms and applications. Clin Dev Immunol. 2012;2012:623474.
  • Bergmann KC, Demoly P, Worm M, et al. Efficacy and safety of sublingual tablets of house dust mite allergen extracts in adults with allergic rhinitis. J Allergy Clin Immunol. 2014;133:1608–1614.e6.
  • 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.e7.
  • Nolte H, Maloney J, Nelson HS, et al. Onset and dose-related efficacy of house dust mite sublingual immunotherapy tablets in an environmental exposure chamber. J Allergy Clin Immunol. 2015;135:1494–1501.e6.
  • Mosbech H, Canonica GW, Becker V, et al. SQ house dust mite sublingually administered immunotherapy tablet (ALK) improves allergic rhinitis in patients with house dust mite allergic asthma and rhinitis symptoms. Ann Allergy Asthma Immunol. 2015;114:134–140.e1.
  • Demoly P, Calderon MA, Casale TB, et al. The value of pre- and co-seasonal sublingual immunotherapy in pollen-induced allergic rhinoconjunctivitis. Clin Trans Allergy. 2015;5(18):eCollection 2015.
  • RAGWITEK (Short Ragweed Pollen Allergen Extract) Tablet for Sublingual Use [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc.; June 2014. cited 2016 Aug 4. Available from: https://www.ragwitek.com/
  • ORALAIR (Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass Mixed Pollens Allergen Extract) Tablet for Sublingual Use [package insert]. Antony, France: Stallergenes S.A.; Oct 2014; cited 2016 Aug 4. Available from: http://www.oralair.com/
  • GRASTEK (Timothy Grass Pollen Extract) Tablet for Sublingual Use [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; June 2014; cited 2016 Aug 4. Available from: https://www.grastek.com/
  • Devillier P, Dreyfus JF, Demoly CM, et al. A meta-analysis of sublingual allergen immunotherapy and pharmacotherapy in pollen-induced seasonal allergic rhinoconjunctivitis. BMC Med. 2014;12:71.
  • Strunk RC, Sternberg AL, Szefler SJ, et al. 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;154:682–687.
  • 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;129:717–725.e5.
  • Marogna M, Spadolini I, Massolo A, et al. Long-lasting effects of sublingual immunotherapy according to its duration: a 15-year prospective study. J Allergy Clin Immunol. 2010;126:969–975.
  • Di Bona D, Plaia A, Scafidi V, et al. Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis. J Allergy Clin Immunol. 2010;126:558–566.
  • Radulovic S, Wilson D, Calderon M, et al. Systematic reviews of sublingual immunotherapy (SLIT). Allergy. 2011;66:740–752.
  • Calderon MA, Penagos M, Sheikh A, et al. Sublingual immunotherapy for allergic conjunctivitis: cochrane systematic review and meta-analysis. Clin Exp Allergy. 2011;41:1263–1272.
  • Lin SY, Erekosima N, Kim JM, et al. Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systemic review [published erratum in: JAMA 2013;310:647. Jama. 2013;309:1278–1288.
  • Dretzke J, Meadows A, Novielli N, et al. Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: A systematic review and indirect comparison. J Allergy Clin Immunol. 2013;131:1361–1366.
  • Durham SR, Penagos M. Sublingual or subcutaneous immunotherapy for allergic rhinitis. J Allergy Clin Immunol. 2016;137:339–349.
  • Maloney J, Bernstein DI, Nelson H, et al. Efficacy and safety of grass sublingual immunotherapy tablet. MK-7243: a large randomized controlled trial. Ann Allergy Asthma Immunol. 2014;112:146–153.e2.
  • Nolte H, Hébert J, Berman G, et al. Randomized controlled trial of ragweed allergy immunotherapy tablet efficacy and safety in North American adults. Ann Allergy Asthma Immunol. 2013;110:450–456.e4.
  • Creticos PS, Maloney J, Bernstein DI, et al. Randomized controlled trial of a ragweed allergy immunotherapy tablet efficacy and safety in North American and European adults. J Allergy Clin Immunol. 2013;131:1342–1349.
  • Calderon MA, Casale TB, Nelson HS, et al. An evidence-based analysis of house dust mite allergen immunotherapy: A call for more rigorous clinical studies. J Allergy Clin Immunol. 2013;132:1322–1336.
  • Klimek L, Mosbech H, Zieglmayer P, et al. SQ house dust mite (HDM) SLIT-tablet provides clinical improvement in HDM-induced allergic rhinitis. Expert Rev Clin Immunol. 2016;12(4):369–377.
  • Canonica GW, Virchow JC, Zieglmayer P, et al. Efficacy and safety of SQ house dust mite (HDM) SLIT-tablet treatment of HDM allergic asthma. Expert Rev Clin Immunol. 2016 Aug;12(8):805–815.
  • Mosbech H, Canonica GW, Backer V, et al. SQ house dust mite sublingually administered immunotherapy tablet (ALK) improves allergic rhinitis in patients with house dust mite allergic asthma and rhinitis symptoms. Ann Allergy Asthma Immunol. 2015;114:134–140.
  • Demoly P, Emminger W, Rehm D, et al. Effective treatment of house dust mite-induced allergic rhinitis with 2 doses of the SQ HDM SLIT-tablet: results from a randomized, double-blind, placebo-controlled phase III trial. J Allergy Clin Immunol. 2016 Feb;137(2):444–451.e8.
  • 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(16):1715–1725.
  • Nolte H, Bernstein DI, Nelson HS, et al. Efficacy of house dust mite sublingual immunotherapy tablet in North American adolescents and adults in a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2016 Aug 10; pii: S0091-6749(16)30783-7. [Epub ahead of print] PubMed PMID: 27521719. DOI: 10.1016/j.jaci.2016.06.044
  • Karakoc-Aydiner E, Eifan AO, Baris S, et al. Long-term effect of sublingual and subcutaneous immunotherapy in dust mite-allergic children with asthma/rhinitis: A 3-year prospective randomized controlled trial. J Investig Allergol Clin Immunol. 2015;25(5):334–342.
  • Durham SR, Creticos PS, Nelson HS, et al. Treatment effect of sublingual immunotherapy tablets and pharmacotherapies for seasonal and perennial allergic rhinitis: pooled analyses. J Allergy Clin Immunol. 2016;pii: S0091-6749(16)30614-5. DOI:10.1016/j.jaci.2016.04.061
  • Maloney J, Berman G, Gagnon R, et al. Sequential treatment initiation with timothy grass and ragweed sublingual immunotherapy tablets followed by simultaneous treatment is well tolerated. J Allergy Clin Immunol Pract. 2016;4(2):301–309.e2.
  • Marogna M, Spadolini I, Massolo A, et al. Effects of sublingual immunotherapy for multiple or single allergens in polysensitized patients. Ann Allergy Asthma Immunol. 2007;98(3):274–280.
  • Moreno-Ancillo A, Moreno C, Ojeda P, et al. Efficacy and quality of life with once-daily sublingual immunotherapy with grasses plus olive pollen extract without updosing. J Investig Allergol Clin Immunol. 2007;17(6):399–405.
  • Amar SM, Harbeck RJ, Sills M, et al. Response to sublingual immunotherapy with grass pollen extract: monotherapy versus combination in a multiallergen extract. J Allergy Clin Immunol. 2009;124(1):150–156.
  • Di Bona DD, Plaia A, Leto-Barone MS, et al. Efficacy of grass pollen allergen sublingual immunotherapy tablets for seasonal allergic rhinoconjunctivitis. JAMA Int Med. 2015;175(8):1301–1309.
  • Cox LS, Linneman DL, Nolte H, et al. Sublingual immunotherapy: a comprehensive review. J Allergy Clin Immunol. 2006;117:1021–1035.
  • Antico A, Fante R. Esophageal hypereosinophilia induced by grass sublingual immunotherapy. J Allergy Clin Immunol. 2014;133(5):1482–1484.
  • Miehlke S, Alpan O, Shröder S, et al. Induction of eosinophilic esophagitis by sublingual pollen immunotherapy. Case Rep Gastroenterol. 2013;7(3):363–368.
  • Normansell R, Kew KM, Bridgman AL. Sublingual immunotherapy for asthma. Cochrane Database Syst Rev. 2015;28(8):CD011293.
  • Nelson HS, Makatsori M, Calderon MA. Subcutaneous immunotherapy and sublingual immunotherapy: comparative efficacy, current and potential indications, and warnings – United States versus Europe. Immunol Allergy Clin North Am. 2016;36:13–24.
  • Senna G, Lombardi C, Canonica GW, et al. How adherent to sublingual immunotherapy prescriptions are patients? The manufacturers’ viewpoint. J Allergy Clin Immunol. 2010;126(3):668–669.
  • Blamoutier P, Blamoutier J, Guibert L. Treatment of pollinosis with pollen extracts by the method of cutaneous quadrille ruling [in French]. Presse Med. 1959;67:2299–2301.
  • 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, 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.
  • Werfel T. Epicutaneous allergen administration: A novel approach for allergen-specific immunotherapy? J Allergy Clin Immunol. 2009;124:1003–1004.
  • Turjanmaa K, Darsow U, Niggemann B, et al. EAACI/GA2-LEN position paper: present status of the atopy patch test. Allergy. 2006;61:1377–1384.
  • Senti G, Johansen P, Erdmann I, et al. Intralymphatic immunotherapy. Curr Opin Allergy Clin Immunol. 2009;9:537–543.
  • Martinez-Gomez JM, Johansen P, Erdmann I, et al. Intralymphatic injections as a new administration of route for allergen-specific immunotherapy. Int Arch Allergy Immunol. 2009;150:59–65.
  • 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 USA. 2008;105:17908–17912.
  • 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.
  • Kundig TM. Immunotherapy concepts under investigation. Allergy. 2011;66:60–62.
  • 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.
  • 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.e5.
  • Marcucci F, Sensi LG, Caffarelli C, et al. Low-dose local nasal immunotherapy in children with perennial allergic rhinitis due to Dermatophagoides. Allergy. 2002;57:23–28.
  • Tsai JJ, Liao EC, Tsai FH, et al. The effect of local nasal immunotherapy in allergic rhinitis: using strips of the allergen Dermatophagoides pteronyssinus. J Asthma. 2009;46:165–170.
  • Reisacher W, Rudner S, Kotik V. Oral mucosal immunotherapy using a toothpaste delivery system for the treatment of allergic rhinitis. Int J Pharm Compd. 2014;18(4):287–290.
  • Van Rijswijk JB, Blom HM, Fokkens WJ. Idiopathic rhinitis, the ongoing quest. Allergy. 2005;60(12):1471–1481.
  • Bernstein JA, Davis BP, Picard JK, et al. A randomized, double-blind, parallel trial comparing capsaicin nasal spray with placebo in subjects with a significant component of nonallergic rhinitis. Ann Allergy Asthma Immunol. 2011;107:171.
  • Ridolo E, Montagni M, Caminati M, et al. Emerging drugs for allergic conjunctivitis. Expert Opin Emerg Drugs. 2014;19(2):291–302.
  • Barchuk WT, Salapatek AM, Ge T, et al. A proof-of-concept study of the effect of the novel H3-receptor antagonist in allergen-induced nasal congestion. J Allergy Clin Immunol. 2013;132(4):838-846.e1-e6.
  • Stokes JR, Romero FA Jr, Allan RJ, et al. The effects of an H3 receptor antagonist (PF-03654746) with fexofenadine on reducing allergic rhinitis symptoms. J Allergy Clin Immunol. 2012;129(2):409-12.e1-2.
  • North ML, Walker TJ, Steacy LM, et al. Add-on histamine receptor-3 antagonist for allergic rhinitis: a double-blind randomized crossover trial using the environmental exposure unit. Allergy Asthma Clin Immunol. 2014;10(1):33.
  • Daley-Yates P, Ambery C, Sweeney L, et al. The efficacy and tolerability of two novel H(1)/H(3) receptor antagonists in seasonal allergic rhinitis. Int Arch Allergy Immunol. 2012;158(1):84–98.
  • Osguthorpe JD. Pathophysiology of and potential new therapies for allergic rhinitis. Int Forum Allergy Rhinol. 2013;3(5):384–392.
  • Raap U, Braunstahl GJ. The role of neurotrophins in the pathophysiology of allergic rhinitis. Curr Opin Allergy Clin Immunol. 2010;10:8–13.
  • Lazewska D, Kiec-Kononowicz K. Azines as histamine H4 receptor antagonists. Front Biosci (Schol Ed). 2012;4:967–987.
  • Valenta R, Niederberoer R. Recombinant allergens for immunotherapy. J Allergy Clin Immunol. 2007;119:826–830.
  • Larche M, Akdis CA, Valenta R. Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol. 2006;6:761–771.
  • Niederberger V, Horak F, Vrtaa S, et al. Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc Natl Acaad Sci USA. 2004;101(Suppl 2):14677–14682.
  • Valenta R, Ferreira F. Focke-Tejkl, et al. From allergen genes to allergen vaccines. Annu Rev Immunol. 2010;28:211–241.
  • 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.
  • Reisenger 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;116:347–354.
  • Niederberger V, Reisenger S, Valent P, et al. Vaccination with genetically modified birch pollen allergens: immune and clinical effects on oral allergy syndrome. J Allergy Clin Immunol. 2007;119:1013–1016.
  • Jutel M, Jäger L, Suck R, et al. Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol. 2005;116:608–613.
  • 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. 2009;122:951–960.
  • Larché M. Update on the current status of peptide immunotherapy. J Allergy Clin Immunol. 2007;119:906–909.
  • Briner TJ, Kuo MC, Keating KM, et al. Peripheral T-cell tolerance. induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergen Fel d I. Proc Natl Acad Sci USA. 1993;90:7608–7612.
  • Wallner BP, Gefter ML. Immunotherapy with T-cell-reactive peptides derived from allergens. Allergy. 1994;49:302–308.
  • 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.
  • Couroux P, Patel D, Armstrong K, et al. Fel d 1-derived synthetic peptide immune-regulatory epitopes show a long-term treatment effect in cat allergic subjects. Clin Exp Allergy. 2015;45(5):974–981.
  • Racila DM, Kline JN. Perspectives in asthma: molecular use of microbial products in asthma prevention and treatment. J Allergy Clin Immunol. 2005;116(6):1202–1205.
  • Tulic MK, Fiset PO, Manoukian JJ, et al. Role of toll-like receptor 4 in protection by bacterial lipopolysaccharide in the nasal mucosa of atopic children but not adults. Lancet. 2004;363(9422):1689–1697.
  • Gawchik SM, Saccar CL. Pollinex Quattro Tree: allergy vaccine. Expert Opin Biol Ther. 2009;9(3):377–382.
  • Baldrick P, Richardson D, Wheeler AW. Safety evaluation of a glutaraldehyde modified tyrosine adsorbed housedust mite extract containing monophosphoryl lipid A (MPL) adjuvant: a new allergy vaccine for dust mite allergy. Vaccine. 2001;20:737–743.
  • Rosewich M, Lee D, Zielen S. Pollinex Quattro: an innovative four injections immunotherapy in allergic rhinitis. Hum Vaccin Immunother. 2013;9(7):1523–1531.
  • Aryan Z, Rezaei N. Toll-like receptors as targets for allergen immunotherapy. Curr Opin Allergy Clin Immunol. 2015;15(6):568–574.
  • Drachenberg KJ, Wheeler AW, Stuebner P, et al. A well-tolerated grass pollen-specific allergy vaccine containing a novel adjuvant, monophosphoryl lipid A, reduces allergic symptoms after only four preseasonal injections. Allergy. 2001;56(6):498–505.
  • Mccormack PL, Wagstaff AJ. Ultra-short-course seasonal allergy vaccine (Pollinex Quattro). Drugs. 2006;66(7):931–938.
  • Zielen S, Metz D, Sommer E, et al. Short-term immunotherapy with allergoids and the adjuvant monophosphoryl lipid a. Results from a 3-year postmarketing surveillance study. Allergologie. 2007;30:S1–9.
  • Rosewich M, Schulze J. Fischer von weikersthal-drachenberg KJ, Zielen S. Ultra-short course immunotherapy in children and adolescents during a 3-yrs post-marketing surveillance study. Pediatr Allergy Immunol. 2010;21(1 Pt 2):e185–9.
  • Casale TB, Kessler J, Romero FA. Safety of the intranasal toll-like receptor 4 agonist CRX-675 in allergic rhinitis. Ann Allergy Asthma Immunol. 2006;97(4):454–456.
  • Pfaar O, Barth C, Jaschke C, et al. Sublingual allergen-specific immunotherapy adjuvanted with monophosphoryl lipid A: a phase I/IIa study. Int Arch Allergy Immunol. 2011;154(4):336–344.
  • Nelson HS. Allergen immunotherapy now and in the future. Allergy Asthma Proc. 2016;37(4):268–272.
  • Tighe H, Takabayashi K, Schwartz D, et al. Conjugation of immunostimulatory DNA to the short ragweed allergen amb a 1 enhances its immunogenicity and reduces its allergenicity. J Allergy Clin Immunol. 2000;106(1 Pt 1):124–134.
  • Higgins D, Rodriguez R, Milley R, et al. Modulation of immunogenicity and allergenicity by controlling the number of immunostimulatory oligonucleotides linked to Amb a 1. J Allergy Clin Immunol. 2006;118(2):504–510.
  • Tulic MK, Fiset PO, Christodoulopoulos P, et al. Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response. J Allergy Clin Immunol. 2004;113(2):235–241.
  • 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(14):1445–1455.
  • Stokes JR, Casale TB. Novel Approaches of Immunotherapy. Curr Treat Options Allergy. 2014;1(1):58–67.
  • 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(4):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(9):1305–1312.
  • Beeh KM, Kanniess F, Wagner F, et al. The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma. J Allergy Clin Immunol. 2013;131(3):866–874.
  • Casale TB, Cole J, Beck E, et al. CYT003, a TLR9 agonist, in persistent allergic asthma - a randomized placebo-controlled Phase 2b study. Allergy. 2015;70(9):1160–1168.
  • Greiff L, Cervin A, Ahlström-Emanuelsson C, et al. Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis. Respir Res. 2012;13:53.
  • Delaney S, Biffen M, Maltby J, et al. Tolerability in man following inhalation dosing of the selective TLR7 agonist, AZD8848. BMJ Open Respir Res. 2016;3(1):e000113.
  • Horak F. VTX-1463, a novel TLR8 agonist for the treatment of allergic rhinitis. Expert Opin Investig Drugs. 2011;20(7):981–986.
  • Henmar H, Lund G, Lund L, et al. Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy. Clin Exp Immunol. 2008;153(3):316–323.
  • 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(6):801–807.
  • Dominicus R. 3-years’ long-term effect of subcutaneous immunotherapy (SCIT) with a high-dose hypoallergenic 6-grass pollen preparation in adults. Eur Ann Allergy Clin Immunol. 2012;44(3):135–140.
  • Pfaar O, Robinson DS, Sager A, et al. Immunotherapy with depigmented-polymerized mixed tree pollen extract: a clinical trial and responder analysis. Allergy. 2010;65(12):1614–1621.
  • Zielen S, Kardos P, Madonini E. Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: a randomized controlled trial. J Allergy Clin Immunol. 2010;126(5):942–949.
  • Nieto García A, Nevot Falcó S, Carrillo Díaz T, et al. Safety of cluster specific immunotherapy with a modified high-dose house dust mite extract. Eur Ann Allergy Clin Immunol. 2013;45(3):78–83.
  • Castillo J, Dimov V. Investigational drugs for the treatment of allergic rhinitis. Expert Opin Investig Drugs. 2014;23(6):823–836.

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