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

allergen allergen-specific immunotherapy birch pollen-associated food allergy syndrome molecular allergy vaccine

Journal

Allergy

ISSN: 1398-9995

Titre abrégé: Allergy

Pays: Denmark

ID NLM: 7804028

Informations de publication

Date de publication:
19 Oct 2023

Historique:

revised: 12 09 2023

received: 20 04 2023

accepted: 25 09 2023

medline: 19 10 2023

pubmed: 19 10 2023

entrez: 19 10 2023

Statut: aheadofprint

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS

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.

Identifiants

DOI: 10.1111/all.15919 PMID: 37855043

pubmed: 37855043

doi: 10.1111/all.15919

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Subventions

Organisme : Austrian Science Fund

Organisme : Megagrants

Informations de copyright

Références

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; in press.

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