دورية أكاديمية
أعرض في EDS

Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy.

التفاصيل البيبلوغرافية
العنوان: Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy.
المؤلفون: Khaitov M; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation.; Pirogov Russian National Research Medical University, Moscow, Russian Federation., Shilovskiy I; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation., Valenta R; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation.; Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.; Department of Clinical Immunology and Allergology, Laboratory of Immunopathology, Sechenov First Moscow State Medical University, Moscow, Russian Federation.; Karl Landsteiner University for Healthcare Sciences, Krems, Austria., Weber M; Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Korneev A; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation., Tulaeva I; Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.; Department of Clinical Immunology and Allergology, Laboratory of Immunopathology, Sechenov First Moscow State Medical University, Moscow, Russian Federation., Gattinger P; Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., van Hage M; Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden., Hofer G; Department of Materials and Environmental Chemistry, University of Stockholm, Stockholm, Sweden., Konradsen JR; Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden., Keller W; Institute of Molecular Biosciences, BioTechMed Graz, University of Graz, Graz, Austria., Akinfenwa O; Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Poroshina A; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation., Ilina N; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation., Fedenko E; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation., Elisyutina O; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation.; Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation., Litovkina A; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation.; Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation., Smolnikov E; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation.; Peoples' Friendship University of Russia (RUDN University), Moscow, Russian Federation., Nikonova A; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation., Rybalkin S; Pirogov Russian National Research Medical University, Moscow, Russian Federation., Aldobaev V; Pirogov Russian National Research Medical University, Moscow, Russian Federation., Smirnov V; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation.; Sechenov First Moscow State Medical University, Moscow, Russian Federation., Shershakova N; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation., Petukhova O; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation., Kudlay D; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation.; Sechenov First Moscow State Medical University, Moscow, Russian Federation., Shatilov A; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation., Timofeeva A; NRC Institute of Immunology, FMBA of Russia, Moscow, Russian Federation., Campana R; Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Udin S; Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks' of the Federal Medical Biological Agency, Moscow, Russian Federation., Skvortsova V; Federal Medical Biological Agency of Russia (FMBA Russia), Moscow, Russian Federation.
المصدر: Allergy [Allergy] 2024 Apr; Vol. 79 (4), pp. 1001-1017. Date of Electronic Publication: 2023 Oct 19.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: Denmark NLM ID: 7804028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1398-9995 (Electronic) Linking ISSN: 01054538 NLM ISO Abbreviation: Allergy Subsets: MEDLINE
أسماء مطبوعة: Publication: Copenhagen : Wiley-Blackwell
Original Publication: Copenhagen, Munksgaard.
مواضيع طبية MeSH: Malus* , Food Hypersensitivity*/prevention & control, Animals ; Humans ; Rabbits ; Betula ; Recombinant Fusion Proteins ; Pollen ; Escherichia coli ; Antigens, Plant ; Immunoglobulin E ; Allergens ; Vaccines, Synthetic ; Immunoglobulin G ; Plant Proteins
مستخلص: Background: IgE cross-sensitization to major birch pollen allergen Bet v 1 and pathogenesis-related (PR10) plant food allergens is responsible for the pollen-food allergy syndrome.
Methods: We designed a recombinant protein, AB-PreS, consisting of non-allergenic peptides derived from the IgE-binding sites of Bet v 1 and the cross-reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB-PreS was expressed in E. coli and purified by chromatography. The allergenic and inflammatory activity of AB-PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB-PreS and birch pollen extract-based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA.
Results: IgE-binding experiments and basophil activation test revealed the hypoallergenic nature of AB-PreS. AB-PreS induced lower T-cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB-PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract-based vaccines. Additionally, immunization with AB-PreS induced HBV-specific antibodies potentially protecting from infection with HBV.
Conclusion: The recombinant AB-PreS-based vaccine is hypoallergenic and superior over currently registered allergen extract-based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals.
(© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
References: Mothes N, Westritschnig K, Valenta R. Tree pollen allergens. Clin Allergy Immunol. 2004;18:165‐184. doi:10.1007/s11882-004-0089-y.
Elisyutina O, Lupinek C, Fedenko E, et al. IgE‐reactivity profiles to allergen molecules in Russian children with and without symptoms of allergy revealed by micro‐array analysis. Pediatr Allergy Immunol. 2020;32:251‐263. doi:10.1111/pai.13354.
Hao G, Zheng Y, Wang Z, et al. High correlation of specific IgE sensitization between birch pollen, soy and apple allergens indicates pollen‐food allergy syndrome among birch pollen allergic patients in northern China. J Zhejiang Univ Sci B. 2016;17:399‐404. doi:10.1631/jzus.B1500279.
D'souza N, Weber M, Sarzsinszky E, et al. The molecular allergen recognition profile in China as basis for allergen‐specific immunotherapy. Front Immunol. 2021;12:12. doi:10.3389/fimmu.2021.719573.
Breiteneder H, Pettenburger K, Bito A, et al. The gene coding for the major birch pollen allergen Betv1, is highly homologous to a pea disease resistance response gene. EMBO J. 1989;8:1935‐1938. doi:10.1002/j.1460-2075.1989.tb03597.x.
Gajhede M, Osmark P, Poulsen FM, et al. X‐ray and NMR structure of bet v 1, the origin of birch pollen allergy. Nat Struct Biol. 1996;3:1040‐1045. doi:10.1038/nsb1296-1040.
Ebner C, Birkner T, Valenta R, et al. Common epitopes of birch pollen and apples—studies by western and northern blot. J Allergy Clin Immunol. 1991;88:588‐594. doi:10.1016/0091-6749(91)90152-E.
Son DY, Scheurer S, Hoffmann A, Haustein D, Vieths S. Pollen‐related food allergy: cloning and immunological analysis of isoforms and mutants of mal d 1, the major apple allergen, and bet v 1, the major birch pollen allergen. Eur J Nutr. 1999;38:201‐215. doi:10.1007/s003940050063.
Ahammer L, Grutsch S, Kamenik AS, Liedl KR, Tollinger M. Structure of the major apple allergen mal d 1. J Agric Food Chem. 2017;65:1606‐1612. doi:10.1021/acs.jafc.6b05752.
Polak D, Vollmann U, Grilo J, et al. Bet v 1‐independent sensitization to major allergens in Fagales pollen: evidence at the T‐cell level. Allergy. 2023;78:743‐751. doi:10.1111/all.15594.
Kazemi‐Shirazi L, Pauli G, Purohit A, et al. Quantitative IgE inhibition experiments with purified recombinant allergens indicate pollen‐derived allergens as the sensitizing agents responsible for many forms of plant food allergy. J Allergy Clin Immunol. 2000;105:116‐125. doi:10.1016/S0091-6749(00)90186-6.
Fritsch R, Bohle B, Vollmann U, et al. Bet v 1, the major birch pollen allergen, and mal d 1, the major apple allergen, cross‐react at the level of allergen‐specific T helper cells. J Allergy Clin Immunol. 1998;102:679‐686. doi:10.1016/S0091-6749(98)70287-8.
Westman M, Lupinek C, Bousquet J, et al. Early childhood IgE reactivity to pathogenesis‐related class 10 proteins predicts allergic rhinitis in adolescence. J Allergy Clin Immunol. 2015;135:1199‐1206.e11. doi:10.1016/j.jaci.2014.10.042.
Akdis C, Akdis M, Boyd S, Sampath V, Galli S, Nadeau K. Allergy: mechanistic insights into new methods of prevention and therapy. Sci Transl Med. 2023;15(679):eadd2563. doi:10.1126/scitranslmed.add2563.
Larché M, Akdis CA, Valenta R. Immunological mechanisms of allergen‐specific immunotherapy. Nat Rev Immunol. 2006;6:761‐771. doi:10.1038/nri1934.
Dorofeeva Y, Shilovskiy I, Tulaeva I, et al. Past, presence, and future of allergen immunotherapy vaccines. Allergy. 2020;76:131‐149. doi:10.1111/all.14300.
Durham SR, Shamji MH. Allergen immunotherapy: past, present and future. Nat Rev Immunol. 2022;23:317‐328. doi:10.1038/s41577-022-00786-1.
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.
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.
Petersen BN, Janniche H, Munch EP, et al. Immunotherapy with partially purified and standardized tree pollen extracts. Allergy. 1988;43:353‐362. doi:10.1111/j.1398-9995.1988.tb00429.x.
Bucher X, Pichler WJ, Dahinden CA, Helbling A. Effect of tree pollen specific, subcutaneous immunotherapy on the oral allergy syndrome to apple and hazelnut. Allergy. 2004;59:1272‐1276. doi:10.1111/j.1398-9995.2004.00626.x.
Incorvaia C, Ridolo E, Mauro M, Russello M, Pastorello E. Allergen immunotherapy for birch‐apple syndrome: what do we know? Immunotherapy. 2017;9:1271‐1278. doi:10.2217/imt-2017-0040.
Zimmer J, Bonertz A, Kaul S, Vieths S. Introduction of general chapters on standard methods for allergen quantification in the European pharmacopoeia. Allergy. 2023;78:923‐927. doi:10.1111/all.15631.
Kiel MA, Röder E, Gerth van Wijk R, Al MJ, Hop WCJ, Rutten‐van Mölken MPMH. Real‐life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy. J Allergy Clin Immunol. 2013;132:353‐360.e2. doi:10.1016/j.jaci.2013.03.013.
Valenta R, Ferreira F, Focke‐Tejkl M, et al. From allergen genes to allergy vaccines. Annu Rev Immunol. 2010;28:211‐241. doi:10.1146/annurev-immunol-030409-101218.
Mohsen MO, Bachmann MF. Virus‐like particle vaccinology, from bench to bedside. Cell Mol Immunol. 2022;19:993‐1011. doi:10.1038/s41423-022-00897-8.
Soh WT, Aglas L, Mueller GA, et al. Multiple roles of Bet v 1 ligands in allergen stabilization and modulation of endosomal protease activity. Allergy. 2019;74:2382‐2393. doi:10.1111/all.13948.
Hufnagl K, Kromp L, Bianchini R, et al. Bet v 1 from birch pollen is a hypoallergen with vitamin D3 in the pocket. Allergy. 2021;76:3801‐3804. doi:10.1111/all.15052.
Valenta R, Campana R, Niederberger V. Recombinant allergy vaccines based on allergen‐derived B cell epitopes. Immunol Lett. 2017;189:19‐26. doi:10.1016/j.imlet.2017.04.015.
Valenta R, Campana R, Focke‐Tejkl M, Niederberger V. Vaccine development for allergen‐specific immunotherapy based on recombinant allergens and synthetic allergen peptides: lessons from the past and novel mechanisms of action for the future. J Allergy Clin Immunol. 2016;137:351‐357. doi:10.1016/j.jaci.2015.12.1299.
Zieglmayer P, Focke‐Tejkl M, Schmutz R, et al. Mechanisms, safety and efficacy of a B cell epitope‐based vaccine for immunotherapy of grass pollen allergy. EBioMedicine. 2016;11:43‐57. doi:10.1016/j.ebiom.2016.08.022.
Niederberger V, Neubauer A, Gevaert P, et al. Safety and efficacy of immunotherapy with the recombinant B‐cell epitope–based grass pollen vaccine BM32. J Allergy Clin Immunol. 2018;142:497‐509.e9. doi:10.1016/j.jaci.2017.09.052.
Gieras A, Cejka P, Blatt K, et al. Mapping of conformational IgE epitopes with peptide‐specific monoclonal antibodies reveals simultaneous binding of different IgE antibodies to a surface patch on the major birch pollen allergen, bet v 1. J Immunol. 2011;186:5333‐5344. doi:10.4049/jimmunol.1000804.
Marth K, Breyer I, Focke‐Tejkl M, et al. A nonallergenic birch pollen allergy vaccine consisting of hepatitis PreS–fused bet v 1 peptides focuses blocking IgG toward IgE epitopes and shifts immune responses to a tolerogenic and Th1 phenotype. J Immunol. 2013;190:3068‐3078. doi:10.4049/jimmunol.1202441.
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.
Edlmayr J, Niespodziana K, Linhart B, et al. A combination vaccine for allergy and rhinovirus infections based on rhinovirus‐derived surface protein VP1 and a nonallergenic peptide of the major timothy grass pollen allergen Phl p 1. J Immunol. 2009;182:6298‐6306. doi:10.4049/jimmunol.0713622.
Fling SP, Gregerson DS. Peptide and protein molecular weight determination by electrophoresis using a high‐molarity tris buffer system without urea. Anal Biochem. 1986;155:83‐88. doi:10.1016/0003-2697(86)90228-9.
Huang H‐J, Resch‐Marat Y, Casset A, et al. IgE recognition of the house dust mite allergen Der p 37 is associated with asthma. J Allergy Clin Immunol. 2022;149:1031‐1043. doi:10.1016/j.jaci.2021.07.040.
Bousquet J, Heinzerling L, Bachert C, et al. Practical guide to skin prick tests in allergy to aeroallergens. Allergy. 2012;67:18‐24. doi:10.1111/j.1398-9995.2011.02728.x.
Karsonova A, Riabova K, Villazala‐Merino S, et al. Highly sensitive ELISA‐based assay for quantification of allergen‐specific IgE antibody levels. Allergy. 2020;75:2668‐2670. doi:10.1111/all.14325.
Roberts G, Xatzipsalti M, Borrego LM, et al. Paediatric rhinitis: position paper of the European academy of allergy and clinical immunology. Allergy. 2013;68:1102‐1116. doi:10.1111/all.12235.
Bousquet J, Schünemann HJ, Togias A, et al. Next‐generation allergic rhinitis and its impact on asthma (ARIA) guidelines for allergic rhinitis based on grading of recommendations assessment, development and evaluation (GRADE) and real‐world evidence. J Allergy Clin Immunol. 2020;145:70‐80.e3. doi:10.1016/j.jaci.2019.06.049.
Global Initiative for Asthma. Global strategy for asthma management and prevention. 2016.
Wollenberg A, Oranje A, Deleuran M, et al. ETFAD/EADV eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. J Eur Acad Dermatology Venereol. 2016;30:729‐747. doi:10.1111/jdv.13599.
Skypala IJ, Calderon MA, Leeds AR, Emery P, Till S, Durham SR. Development and validation of a structured questionnaire for the diagnosis of oral allergy syndrome in subjects with seasonal allergic rhinitis during the UK birch pollen season. Clin Exp Allergy. 2011;41:1001‐1011. doi:10.1111/j.1365-2222.2011.03759.x.
Elisyutina O, Fedenko E, Campana R, et al. Bet v 1‐specific IgE levels and PR10 reactivity discriminate silent sensitization from phenotypes of birch allergy. Allergy. 2019;74:2525‐2528. doi:10.1111/all.13931.
Focke M, Linhart B, Hartl A, et al. Non‐anaphylactic surface‐exposed peptides of the major birch pollen allergen, bet v 1, for preventive vaccination. Clin Exp Allergy. 2004;34:1525‐1533. doi:10.1111/j.1365-2222.2004.02081.x.
Litovkina A, Byazrova M, Smolnikov E, et al. Allergic sensitization to mal d 1 without detectable specific serum IgE. Pediatr Allergy Immunol. 2022;33:e13891. doi:10.1111/pai.13891.
Rodríguez‐Domínguez A, Berings M, Rohrbach A, et al. Molecular profiling of allergen‐specific antibody responses may enhance success of specific immunotherapy. J Allergy Clin Immunol. 2020;146:1097‐1108. doi:10.1016/j.jaci.2020.03.029.
Cornelius C, Schöneweis K, Georgi F, et al. Immunotherapy with the preS‐based grass pollen allergy vaccine BM32 induces antibody responses protecting against hepatitis B infection. EBioMedicine. 2016;11:58‐67. doi:10.1016/j.ebiom.2016.07.023.
Huang HJ, Curin M, Banerjee S, et al. A hypoallergenic peptide mix containing T cell epitopes of the clinically relevant house dust mite allergens. Allergy. 2019;74:2461‐2478. doi:10.1111/all.13956.
Sobczak JM, Krenger PS, Storni F, et al. The next generation virus‐like particle platform for the treatment of peanut allergy. Allergy. 2023;78:1980‐1996. doi:10.1111/all.15704.
Tulaeva I, Cornelius C, Zieglmayer P, et al. Quantification, epitope mapping and genotype cross‐reactivity of hepatitis B preS‐specific antibodies in subjects vaccinated with different dosage regimens of BM32. EBioMedicine. 2020;59:102953. doi:10.1016/j.ebiom.2020.102953.
Diem L, Neuherz B, Rohrhofer J, et al. Real‐life evaluation of molecular multiplex IgE test methods in the diagnosis of pollen associated food allergy. Allergy. 2022;77:3028‐3040. doi:10.1111/all.15329.
Gadermaier E, Flicker S, Aberer W, et al. Analysis of the antibody responses induced by subcutaneous injection immunotherapy with birch and Fagales pollen extracts adsorbed onto aluminum hydroxide. Int Arch Allergy Immunol. 2010;151(1):17‐27. doi:10.1159/000232567.
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(5):951‐960. doi:10.1016/j.jaci.2008.09.017.
Niederberger V, Reisinger J, Valent P, et al. Vaccination with genetically modified birch pollen allergens: immune and clinical effects on oral allergy syndrome. J Allergy Clin Immunol. 2007;119(4):1013‐1016. doi:10.1016/j.jaci.2006.12.661.
Paul WE, Katz DH, Goidl EA, Benacerraf B. Carrier function in anti‐hapten immune responses. II. Specific properties of carrier cells capable of enhancing anti‐hapten antibody responses. J Exp Med. 1970;132(2):283‐299. doi:10.1084/jem.132.2.283.
Hofer H, Asam C, Hauser M, et al. Tackling Bet v 1 and associated food allergies with a single hybrid protein. J Allergy Clin Immunol. 2017;140(2):525‐533.e10. doi:10.1016/j.jaci.2016.09.055.
Purohit A, Niederberger V, Kronqvist M, et al. Clinical effects of immunotherapy with genetically modified recombinant birch pollen bet v 1 derivatives. Clin Exp Allergy. 2008;38(9):1514‐1525. doi:10.1111/j.1365-2222.2008.03042.x.
Campana R, Mothes N, Rauter I, et al. Non‐IgE‐mediated chronic allergic skin inflammation revealed with rBet v 1 fragments. J Allergy Clin Immunol. 2008;121(2):528‐530.e1. doi:10.1016/j.jaci.2007.09.014.
Campana R, Moritz K, Marth K, et al. Frequent occurrence of T cell‐mediated late reactions revealed by atopy patch testing with hypoallergenic rBet v 1 fragments. J Allergy Clin Immunol. 2016;137(2):601‐609.e8. doi:10.1016/j.jaci.2015.08.042.
Jahn‐Schmid B, Radakovics A, Lüttkopf D, et al. Bet v 1142‐156 is the dominant T‐cell epitope of the major birch pollen allergen and important for cross‐reactivity with bet v 1‐related food allergens. J Allergy Clin Immunol. 2005;116(1):213‐219. doi:10.1016/j.jaci.2005.04.019.
Brazhnikov G, Smolnikov E, Litovkina A, et al. Natural human bet v 1‐specific IgG antibodies recognize non‐conformational epitopes whereas IgE reacts with conformational epitopes. Allergy. 2023;78:3136‐3153.
Tulaeva I, Kratzer B, Campana R, et al. Preventive allergen‐specific vaccination against allergy: Mission possible? Front Immunol. 2020;11:1368. doi:10.3389/fimmu.2020.01368.
Neurath AR, Kent SB, Parker K, et al. Antibodies to a synthetic peptide from the preS 120–145 region of the hepatitis B virus envelope are virus neutralizing. Vaccine. 1986;4:35‐37. doi:10.1016/s0264-410x(86)80001-9.
Glebe D, Aliakbari M, Krass P, Knoop EV, Valerius KP, Gerlich WH. Pre‐S1 antigen‐dependent infection of tupaia hepatocyte cultures with human hepatitis B virus. J Virol. 2003;77:9511‐9521. doi:10.1128/JVI.77.17.9511-9521.2003.
Gerlich WH. Prophylactic vaccination against hepatitis B: achievements, challenges and perspectives. Med Microbiol Immunol (Berl). 2015;204:39‐55. doi:10.1007/s00430-014-0373-y.
معلومات مُعتمدة: Austrian Science Fund; Megagrants
فهرسة مساهمة: Keywords: allergen; allergen‐specific immunotherapy; birch pollen‐associated food allergy syndrome; molecular allergy vaccine
المشرفين على المادة: 0 (Recombinant Fusion Proteins)
0 (Antigens, Plant)
37341-29-0 (Immunoglobulin E)
0 (Allergens)
0 (Vaccines, Synthetic)
0 (Immunoglobulin G)
0 (Plant Proteins)
تواريخ الأحداث: Date Created: 20231019 Date Completed: 20240401 Latest Revision: 20240710
رمز التحديث: 20240710
DOI: 10.1111/all.15919
PMID: 37855043
قاعدة البيانات: MEDLINE
الوصف
تدمد:1398-9995
DOI:10.1111/all.15919