Extract-Shaped Immune Repertoires as Source for Nanobody-Based Human IgE in Grass Pollen Allergy.
Allergens
Diagnostics
Nanobodies
Standardisation
Timothy grass extract
Journal
Molecular biotechnology
ISSN: 1559-0305
Titre abrégé: Mol Biotechnol
Pays: Switzerland
ID NLM: 9423533
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
06
12
2022
accepted:
11
01
2023
medline:
23
8
2023
pubmed:
26
1
2023
entrez:
25
1
2023
Statut:
ppublish
Résumé
The presence of allergen-specific IgE in serum is a biomarker for allergic disease. Specific IgE antibodies for research and diagnostics, however, remain scarce. In contrast to prototypic antibodies, camelid species have evolved single domains as moiety for antigen recognition. These so-called nanobodies represent a versatile platform for the development of diagnostic and therapeutic approaches. In this study, we aimed for generating nanobodies and derived IgE formats from an extract-shaped immune repertoire. Timothy grass pollen represents a complex, but well-defined mixture of individual allergens. Therefore, a repertoire library from a timothy grass pollen extract immunised llama was established. The selection by phage display yielded 3 nanobodies with immunoreactivity to the extract. IgE-like nanobody-based human IgE (nb-hIgE) antibodies were produced in mammalian cells and assessed in different immunoassays and commercial platforms. Immunoblotting and diagnostic ImmunoCap analysis of single timothy grass pollen allergens identified the major allergens Phl p 6 and Phl p 4 as targets. Assessment of immunoreactivity further documented significant molecular cross-reactivity with pollen extract of different grass species and variant presence of allergens within extracts of Pooideae grasses. In summary, our study shows that extract-based immunisation enables the generation of allergen-specific nanobodies and derived nb-hIgE formats linking nanobody technologies with allergological applications.
Identifiants
pubmed: 36696011
doi: 10.1007/s12033-023-00664-8
pii: 10.1007/s12033-023-00664-8
doi:
Substances chimiques
Single-Domain Antibodies
0
Allergens
0
Immunoglobulin E
37341-29-0
Plant Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1518-1527Subventions
Organisme : Novo Nordisk Fonden
ID : 19OC0058484
Organisme : Danmarks Frie Forskningsfond
ID : 9041-00291A
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Finkelman, F. D., Boyce, J. A., Vercelli, D., & Rothenberg, M. E. (2010). Key advances in mechanisms of asthma, allergy, and immunology in 2009. The Journal of Allergy and Clinical Immunology, 125, 312–318.
pubmed: 20159240
doi: 10.1016/j.jaci.2009.12.936
Gould, H. J., & Sutton, B. J. (2008). IgE in allergy and asthma today. Nature reviews. Immunology, 8, 205–217.
pubmed: 18301424
doi: 10.1038/nri2273
Chang, T. W. (2000). The pharmacological basis of anti-IgE therapy. Nature Biotechnology, 18, 157–162.
pubmed: 10657120
doi: 10.1038/72601
Clement, M. J., Fortune, A., Phalipon, A., Marcel-Peyre, V., Simenel, C., Imberty, A., Delepierre, M., & Mulard, L. A. (2006). Toward a better understanding of the basis of the molecular mimicry of polysaccharide antigens by peptides: The example of Shigella flexneri 5a. Journal of Biological Chemistry, 281, 2317–2332.
pubmed: 16251186
doi: 10.1074/jbc.M510172200
Andersson, K., & Lidholm, J. (2003). Characteristics and immunobiology of grass pollen allergens. International Archives of Allergy and Immunology, 130, 87–107.
pubmed: 12673063
doi: 10.1159/000069013
Dewitt, A. M., Andersson, K., Peltre, G., & Lidholm, J. (2006). Cloning, expression and immunological characterization of full-length timothy grass pollen allergen Phl p 4, a berberine bridge enzyme-like protein with homology to celery allergen Api g 5. Clinical and Experimental Allergy, 36, 77–86.
pubmed: 16393269
doi: 10.1111/j.1365-2222.2006.02399.x
Platts-Mills, T. A., Hilger, C., Jappe, U., Hage, M., Gadermaier, G., Spillner, E., Jonas, L., Keshavarz, B., Aalberse, R. C., Van Ree, R., Goodman, R. E., & Pomes, A. (2021). Carbohydrate epitopes currently recognized as targets for IgE antibodies. Allergy, 76, 2383.
pubmed: 33655520
doi: 10.1111/all.14802
Plum, M., Tjerrild, L., Raiber, T., Bantleon, F., Bantleon, S., Miehe, M., Jabs, F., Seismann, H., Mobs, C., Pfutzner, W., Jakob, T., Andersen, G. R., & Spillner, E. (2022). Structural and functional analyses of antibodies specific for modified core N-glycans suggest a role in TH 2 responses. Allergy, 78, 121–130.
pubmed: 35726192
doi: 10.1111/all.15417
Aalberse, R. C., Koshte, V., & Clemens, J. G. (1981). Immunoglobulin E antibodies that crossreact with vegetable foods, pollen, and Hymenoptera venom. The Journal of Allergy and Clinical Immunology, 68, 356–364.
pubmed: 7298999
doi: 10.1016/0091-6749(81)90133-0
Kohler, J., Blank, S., Muller, S., Bantleon, F., Frick, M., Huss-Marp, J., Lidholm, J., Spillner, E., & Jakob, T. (2014). Component resolution reveals additional major allergens in patients with honeybee venom allergy. Journal of Allergy and Clinical Immunology, 133, 1383–1389.
pubmed: 24440283
doi: 10.1016/j.jaci.2013.10.060
Akdis, C. A., & Akdis, M. (2014). Mechanisms of immune tolerance to allergens: Role of IL-10 and Tregs. The Journal of Clinical Investigation, 124, 4678–4680.
pubmed: 25365074
pmcid: 4347251
doi: 10.1172/JCI78891
Boonpiyathad, T., Meyer, N., Moniuszko, M., Sokolowska, M., Eljaszewicz, A., Wirz, O. F., Tomasiak-Lozowska, M. M., Bodzenta-Lukaszyk, A., Ruxrungtham, K., & van de Veen, W. (2017). High-dose bee venom exposure induces similar tolerogenic B-cell responses in allergic patients and healthy beekeepers. Allergy, 72, 407–415.
pubmed: 27341567
doi: 10.1111/all.12966
Meiler, F., Zumkehr, J., Klunker, S., Ruckert, B., Akdis, C. A., & Akdis, M. (2008). In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure. Journal of Experimental Medicine, 205, 2887–2898.
pubmed: 19001136
pmcid: 2585856
doi: 10.1084/jem.20080193
Shamji, M., & Durham, S. (2017). Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers. The Journal of Allergy and Clinical Immunology, 140, 1485–1498.
pubmed: 29221580
doi: 10.1016/j.jaci.2017.10.010
Shamji, M. H., Ljorring, C., Francis, J. N., Calderon, M. A., Larche, M., Kimber, I., Frew, A. J., Ipsen, H., Lund, K., Wurtzen, P. A., & Durham, S. R. (2012). Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy. Allergy, 67, 217–226.
pubmed: 22077562
doi: 10.1111/j.1398-9995.2011.02745.x
Hamers-Casterman, C., Atarhouch, T., Muyldermans, S., Robinson, G., Hamers, C., Songa, E. B., Bendahman, N., & Hamers, R. (1993). Naturally occurring antibodies devoid of light chains. Nature, 363, 446–448.
pubmed: 8502296
doi: 10.1038/363446a0
Ward, E. S., Gussow, D., Griffiths, A. D., Jones, P. T., & Winter, G. (1989). Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli. Nature, 341, 544–546.
pubmed: 2677748
doi: 10.1038/341544a0
Konning, D., Zielonka, S., Grzeschik, J., Empting, M., Valldorf, B., Krah, S., Schroter, C., Sellmann, C., Hock, B., & Kolmar, H. (2016). Camelid and shark single domain antibodies: Structural features and therapeutic potential. Current Opinion in Structural Biology, 45, 10–16.
pubmed: 27865111
doi: 10.1016/j.sbi.2016.10.019
Zavrtanik, U., Lukan, J., Loris, R., Lah, J., & Hadzi, S. (2018). Structural basis of epitope recognition by heavy-chain camelid antibodies. Journal of Molecular Biology, 430, 4369–4386.
pubmed: 30205092
doi: 10.1016/j.jmb.2018.09.002
Detalle, L., Stohr, T., Palomo, C., Piedra, P. A., Gilbert, B. E., Mas, V., Millar, A., Power, U. F., Stortelers, C., Allosery, K., Melero, J. A., & Depla, E. (2015). Generation and characterization of ALX-0171, a potent novel therapeutic nanobody for the treatment of respiratory syncytial virus infection. Antimicrobial agents and chemotherapy, 60, 6–13.
pubmed: 26438495
pmcid: 4704182
doi: 10.1128/AAC.01802-15
Fahy, J. V., Cockcroft, D. W., Boulet, L. P., Wong, H. H., Deschesnes, F., Davis, E. E., Ruppel, J., Su, J. Q., & Adelman, D. C. (1999). Effect of aerosolized anti-IgE (E25) on airway responses to inhaled allergen in asthmatic subjects. American Journal of Respiratory and Critical Care Medicine, 160, 1023–1027.
pubmed: 10471635
doi: 10.1164/ajrccm.160.3.9810012
Braren, I., Blank, S., Seismann, H., Deckers, S., Ollert, M., Grunwald, T., & Spillner, E. (2007). Generation of human monoclonal allergen-specific IgE and IgG antibodies from synthetic antibody libraries. Clinical Chemistry, 53, 837–844.
pubmed: 17395713
doi: 10.1373/clinchem.2006.078360
Hecker, J., Diethers, A., Etzold, S., Seismann, H., Michel, Y., Plum, M., Bredehorst, R., Blank, S., Braren, I., & Spillner, E. (2011). Generation and epitope analysis of human monoclonal antibody isotypes with specificity for the timothy grass major allergen Phl p 5a. Molecular Immunology, 48, 1236–1244.
pubmed: 21474184
doi: 10.1016/j.molimm.2011.03.005
Hecker, J., Diethers, A., Schulz, D., Sabri, A., Plum, M., Michel, Y., Mempel, M., Ollert, M., Jakob, T., Blank, S., Braren, I., & Spillner, E. (2012). An IgE epitope of Bet v 1 and fagales PR10 proteins as defined by a human monoclonal IgE. Allergy, 67, 1530–1537.
pubmed: 23066955
Plum, M., Michel, Y., Wallach, K., Raiber, T., Blank, S., Bantleon, F. I., Diethers, A., Greunke, K., Braren, I., Hackl, T., Meyer, B., & Spillner, E. (2011). Close-up of the immunogenic alpha1,3-galactose epitope as defined by a monoclonal chimeric immunoglobulin E and human serum using saturation transfer difference (STD) NMR. Journal of Biological Chemistry, 286, 43103–43111.
pubmed: 21990360
pmcid: 3234835
doi: 10.1074/jbc.M111.291823
Aagaard, J. B., Sivelle, C., Fischer, M., Byskov, K., Laursen, N. S., Pfutzner, W., Jakob, T., Mobs, C., Miehe, M., & Spillner, E. (2022). Nanobody-based human antibody formats act as IgE surrogate in hymenoptera venom allergy. Allergy, 77, 2859–2862.
pubmed: 35643911
doi: 10.1111/all.15391
Jabs, F., Plum, M., Laursen, N. S., Jensen, R. K., Molgaard, B., Miehe, M., Mandolesi, M., Rauber, M. M., Pfutzner, W., Jakob, T., Mobs, C., Andersen, G. R., & Spillner, E. (2018). Trapping IgE in a closed conformation by mimicking CD23 binding prevents and disrupts FcepsilonRI interaction. Nature Communications, 9, 7.
pubmed: 29295972
pmcid: 5750235
doi: 10.1038/s41467-017-02312-7
Zettl, I., Ivanova, T., Zghaebi, M., Rutovskaya, M. V., Ellinger, I., Goryainova, O., Kollarova, J., Villazala-Merino, S., Lupinek, C., Weichwald, C., Drescher, A., Eckl-Dorna, J., Tillib, S. V., & Flicker, S. (2022). Generation of high affinity ICAM-1-specific nanobodies and evaluation of their suitability for allergy treatment. Frontiers in Immunology, 13, 1022418.
pubmed: 36439110
pmcid: 9682242
doi: 10.3389/fimmu.2022.1022418
Akiba, H., Tamura, H., Kiyoshi, M., Yanaka, S., Sugase, K., Caaveiro, J. M. M., & Tsumoto, K. (2019). Structural and thermodynamic basis for the recognition of the substrate-binding cleft on hen egg lysozyme by a single-domain antibody. Scientific Reports, 9, 15481.
pubmed: 31664051
pmcid: 6820745
doi: 10.1038/s41598-019-50722-y
Chen, F., Ma, H., Li, Y., Wang, H., Samad, A., Zhou, J., Zhu, L., Zhang, Y., He, J., Fan, X., & Jin, T. (2019). Screening of nanobody specific for peanut major allergen Ara h 3 by phage display. Journal of Agricultural and Food Chemistry, 67, 11219–11229.
pubmed: 31408330
doi: 10.1021/acs.jafc.9b02388
Hu, Y., Wu, S., Wang, Y., Lin, J., Sun, Y., Zhang, C., Gu, J., Yang, F., Lv, H., Ji, X., Zhang, Y., Muyldermans, S., & Wang, S. (2021). Unbiased immunization strategy yielding specific nanobodies against macadamia allergen of vicilin-like protein for immunoassay development. Journal of Agricultural and Food Chemistry, 69, 5178–5188.
pubmed: 33882666
doi: 10.1021/acs.jafc.1c00390
Zettl, I., Ivanova, T., Strobl, M. R., Weichwald, C., Goryainova, O., Khan, E., Rutovskaya, M. V., Focke-Tejkl, M., Drescher, A., Bohle, B., Flicker, S., & Tillib, S. V. (2021). Isolation of nanobodies with potential to reduce patients IgE binding to Bet v 1 (68/100 characters). Allergy, 77, 1751–1760.
pubmed: 34837242
doi: 10.1111/all.15191
Matricardi, P. M., Kleine-Tebbe, J., Hoffmann, H. J., Valenta, R., Hilger, C., Hofmaier, S., Aalberse, R. C., Agache, I., Asero, R., Ballmer-Weber, B., Barber, D., Beyer, K., Biedermann, T., Bilo, M. B., Blank, S., Bohle, B., Bosshard, P. P., Breiteneder, H., Brough, H. A., et al. (2016). EAACI molecular allergology user’s guide. Pediatric Allergy and Immunology, 27(Suppl 23), 1–250.
pubmed: 27288833
doi: 10.1111/pai.12563
Offermann, N., Plum, M., Hubner, U., Rathloff, K., Braren, I., Fooke, M., & Spillner, E. (2016). Human serum substitution by artificial sera of scalable allergen reactivity based on polyclonal antibodies and chimeras of human FcgammaRI and IgE domains. Allergy, 71, 1794–1799.
pubmed: 27588368
doi: 10.1111/all.13038
Wood, R. A., Segall, N., Ahlstedt, S., & Williams, P. B. (2007). Accuracy of IgE antibody laboratory results. Annals of Allergy, Asthma & Immunology, 99, 34–41.
doi: 10.1016/S1081-1206(10)60618-7
Popescu, F. D. (2014). Molecular biomarkers for grass pollen immunotherapy. World Journal of Methodology, 4, 26–45.
pubmed: 25237628
pmcid: 4145574
doi: 10.5662/wjm.v4.i1.26
Vrtala, S., Fischer, S., Grote, M., Vangelista, L., Pastore, A., Sperr, W. R., Valent, P., Reichelt, R., Kraft, D., & Valenta, R. (1999). Molecular, immunological, and structural characterization of Phl p 6, a major allergen and P-particle-associated protein from Timothy grass (Phleum pratense) pollen. The Journal of Immunology, 163, 5489–5496.
pubmed: 10553075
doi: 10.4049/jimmunol.163.10.5489
Zafred, D., Nandy, A., Pump, L., Kahlert, H., & Keller, W. (2013). Crystal structure and immunologic characterization of the major grass pollen allergen Phl p 4. The Journal of Allergy and Clinical Immunology, 132, 696–703.
pubmed: 23683465
doi: 10.1016/j.jaci.2013.03.021
Westman, M., Aberg, K., Apostolovic, D., Lupinek, C., Gattinger, P., Mittermann, I., Andersson, N., Melen, E., Bergstrom, A., Anto, J. M., Bousquet, J., Valenta, R., Wickman, M., van Hage, M., Mechanisms for the Development of Allergies, c. (2020). Sensitization to grass pollen allergen molecules in a birth cohort-natural Phl p 4 as an early indicator of grass pollen allergy. The Journal of Allergy and Clinical Immunology, 145, 1174–1181.
pubmed: 31954777
doi: 10.1016/j.jaci.2020.01.006
Madeira, F., Pearce, M., Tivey, A. R. N., Basutkar, P., Lee, J., Edbali, O., Madhusoodanan, N., Kolesnikov, A., & Lopez, R. (2022). Search and sequence analysis tools services from EMBL-EBI in 2022. Nucleic Acids Research, 50, W1.
doi: 10.1093/nar/gkac240
Waterhouse, A. M., Procter, J. B., Martin, D. M., Clamp, M., & Barton, G. J. (2009). Jalview Version 2–a multiple sequence alignment editor and analysis workbench. Bioinformatics, 25, 1189–1191.
pubmed: 19151095
pmcid: 2672624
doi: 10.1093/bioinformatics/btp033