Rational Design of Hypoallergenic Vaccines: Blocking IgE-binding to Polcalcin Using Allergen-specific IgG Antibodies

  • Mohsen Mohammadi Mail The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
  • Gholamreza Khamisipour Department of Hematology, Faculty of Allied Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
  • Faezeh Soltanpour Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran
  • Fatemeh Omrani The Persian Gulf Healthy Research Center, Bushehr University of Medical Sciences, Bushehr, Iran
  • Behrooz Taheri Department of Medical Laboratory Sciences, School of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  • Niloofar Momenzadeh The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
  • Moradali Fouladvand Department of Microbiology and Parasitology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
Keywords:
Chenopodium album, Immunotherapy, Polcalcin, Recombinant fusion proteins, Vaccine

Abstract

Chenopodium album polcalcin (Che a 3) is characterized as a major cause of cross-reactivity inallergic patients to the Chenopodiaceae family. Therefore, the present study was conducted to develop a hypoallergenic Che a 3 derivatives as the candidate vaccine for type 1 allergy.
Four derivatives were generated from Che a 3. The first was a mosaic peptide derivative computationally identified in Che a 3 which was coupled to keyhole limpet hemocyanin (KLH). The second one was a mutant Che a 3, and the other two derivatives included N- and C-terminal halves of Che a 3 that both coupled to KLH. The IgE-binding capacity of Che a 3 and its derivatives and also their ability to induce there combinant Che a 3 (rChe a 3)-specific IgG antibody, were determined using the enzyme-linked immune sorbent assay (ELISA). Moreover, the lymphopro liferative capacity of rChe a 3 or its derivatives and their pro-inflammatory cytokine response interleukin (IL)-5 and IL-13 were measured in the human peripheral blood mononuclear cells (PBMCs).
Among all derivatives, the N-terminal half peptide and mosaic peptide exhibited the lowest IgEbinding capacity. In addition, in comparison to other antigens, KLH-coupled mosaic peptide induced the highest level of the recombinant Che a 3 (rChe a 3)-specific IgG antibody and ther Che a 3 specific-blocking IgG antibody in mice. Moreover, the mosaic peptide lacked lymphopro liferative capacity and down-regulated expression of pro-allergic IL-5 and IL-13 cytokines.

References

1. Genuneit J, Seibold A, Apfelbacher C, Konstantinou G, Koplin J, La Grutta S, et al. Overview of systematic reviews in allergy epidemiology. Allergy. 2017;72(6):849-56.
2. Focke-Tejkl M, Valenta R. Safety of engineered allergen-specific immunotherapy vaccines. Curr Opin Allergy Clin Immunol. 2012;12(5):555.
3. Shoormasti RS, Sabetkish N, Kazemnejad A, Vahabi N, Fazlollahi MR, Pourpak Z, et al. A meta-analysis of sensitization to the most common aeroallergens in a Middle Eastern region: an overview of the main molecular allergens. Aerobiologia. 2019:1-27.
4. Fereidouni M. Aeroallergen sensitivity of Iranian patients with allergic rhinitis. Proceedings of EAACI Summer School, Hanover, Germany, 2006.
5. Barderas R, Villalba M, Lombardero M, Rodríguez R. Identification and characterization of Che a 1 allergen from Chenopodium album pollen. Int Arch Allergy Immunol. 2002;127(1):47-54.
6. Almogren A. Airway allergy and skin reactivity to aeroallergens in Riyadh. Saudi Med J. 2009;30(3):392-6.
7. Verdino P, Barderas R, Villalba M, Westritschnig K, Valenta R, Rodriguez R, et al. Three-dimensional structure of the cross-reactive pollen allergen Che a 3: visualizing cross-reactivity on the molecular surfaces of weed, grass, and tree pollen allergens. J Immunol. 2008;180(4):2313-21.
8. San Nicoló M, Braun T, Eder K, Berghaus A, Gröger M. Clinical relevance of IgE to profilin and/or polcalcin in pollen-sensitized patients. Int Arch Allergy Immunol. 2016;169(2):101-7.
9. Focke-Tejkl M, Weber M, Niespodziana K, Neubauer A, Huber H, Henning R, et al. Development and characterization of a recombinant, hypoallergenic, peptide-based vaccine for grass pollen allergy. J Allergy Clin Immunol. 2015;135(5):1207-17. e11.
10. 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(2):351-7.
11. Westritschnig K, Focke M, Verdino P, Goessler W, Keller W, Twardosz A, et al. Generation of an allergy vaccine by disruption of the three-dimensional structure of the cross-reactive calcium-binding allergen, Phl p 7. J Immunol. 2004;172(9):5684-92.
12. Alsamarai A, Alobaidi A, Alwan A, Abdulaziz Z, Dawood Z. Systemic adverse reaction to specific immunotherapy. J Aller Ther. 2011;2(111):2.
13. Twaroch TE, Focke M, Civaj V, Weber M, Balic N, Mari A, et al. Carrier-bound, nonallergenic Ole e 1 peptides for vaccination against olive pollen allergy. J Allergy ClinImmunol. 2011;128(1):178-84. e7.
14. Twaroch T, Focke M, Fleischmann K, Balic N, Lupinek C, Blatt K, et al. Carrier‐bound Alt a 1 peptides without allergenic activity for vaccination against Alternariaalternata allergy. Clin Exp Allergy. 2012;42(6):966-75.
15. Coop CA. Local reactions from subcutaneous allergen immunotherapy. Immunotherapy. 2013;5(12):1339-45.
16. Gilissen LJ, Bolhaar ST, Knulst AC, Zuidmeer L, Van Ree R, Gao Z, et al. editors. Production of hypoallergenic plant foods by selection, breeding and genetic modification. Allergy Matters: new approaches to allergy prevention and management: The International Conference on Allergy Prevention, Wageningen, The Netherlands 4-6 February 2004; 2006: Springer-Life Sciences.
17. Watanabe M, Watanabe J, SoNoYAMA K, Tanabe S. Novel method for producing hypoallergenic wheat flour by enzymatic fragmentation of the constituent allergens and its application to food processing. BiosciBiotechnolBiochem. 2000;64(12):2663-7.
18. Zieglmayer P, Focke-Tejkl M, Schmutz R, Lemell P, Zieglmayer R, Weber M, et al. Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy. E Bio Medicine. 2016;11:43-57.
19. Campana R, Moritz K, Marth K, Neubauer A, Huber H, Henning R, 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):601-9. e8.
20. Schmitz N, Dietmeier K, Bauer M, Maudrich M, UtzingerS, Muntwiler S, et al. Displaying Fel d1 on virus-like particles prevents reactogenicity despite greatly enhanced immunogenicity: a novel therapy for cat allergy. J Exp Med. 2009;206(9):1941-55.
21. Cornelius C, Schöneweis K, Georgi F, Weber M, Niederberger V, Zieglmayer P, et al. Immunotherapy with the PreS-based grass pollen allergy vaccine BM32 induces antibody responses protecting against hepatitis B infection. E Bio Medicine. 2016;11:58-67.
22. Curin M, Khaitov M, Karaulov A, Namazova-Baranova L, Campana R, Garib V, et al. Next-generation of allergen-specific immunotherapies: molecular approaches. Curr Allergy Asthma Rep. 2018;18(7):39.
23. Roozbehani M, Falak R, Mohammadi M, Hemphill A, Razmjou E, RezaMeamar A, et al. Characterization of a multi-epitope peptide with selective MHC-binding capabilities encapsulated in PLGA nanoparticles as a novel vaccine candidate against Toxoplasma gondii infection. Vaccine. 2018;36(41):6124-32.
24. Asadi-Ghalehni M, Rasaee MJ, Javanmardi M, Khalili S, Mohamadi M, Fatemi F. In silico and in vitro evaluation of a recombinant fusion peptide as a novel candidate vaccine for EGFR-positive tumors.Biosci. Biotechnol Res Asia. 2015;12(3):2405-10.
25. Fanuel S, Tabesh S, Mokhtarian K, Saroddiny E, Fazlollahi MR, Pourpak Z, et al. Construction of a recombinant B-cell epitope vaccine based on a Der p1-derived hypoallergen: a bioinformatics approach. Immunotherapy. 2018;10(7):537-53.
26. Mohammadi M, Mokhtarian K, Kardar GA, Farrokhi S, Sadroddiny E, Khorramizadeh MR, et al. Expression of recombinant parvalbumin from wolf-herring fish and determination of its IgE-binding capability. Food AgricImmunol. 2017;28(4):573-85.
27. Mohammadi M, Falak R, Mokhtarian K, Khoramizadeh MR, Sadroddiny E, Kardar GA. Identification and characterization of main allergic proteins in cooked wolf herring fish. Iran J Allergy Asthma Immunol. 2016;15(5):363.
28. Moghaddam MV, Fallahpour M, Mohammadi M, Varaee FR, Mokhtarian K, Khoshmirsafa M, et al. Identification of polcalcin as a novel allergen of Amaranthusretroflexus pollen. Allergol Immunopathol (Madr). 2019.
29. Mohammadi M, Taheri B, Momenzadeh N, Salarinia R, Nabipour I, Farshadzadeh Z, et al. Identification and Characterization of Novel Antimicrobial Peptide from Hippocampus comes by In Silico and Experimental Studies. Mar Biotechnol. 2018:1-11.
30. Vrtala S, Akdis CA, Budak F, Akdis M, Blaser K, Kraft D, et al. T cell epitope-containing hypoallergenic recombinant fragments of the major birch pollen allergen, Bet v 1, induce blocking antibodies. J Immunol. 2000;165(11):6653-9.
31. Van Neerven R, Knol E, Ejrnaes A, Würtzen P. IgE-mediated allergen presentation and blocking antibodies: regulation of T-cell activation in allergy. Int Arch Allergy Immunol. 2006;141(2):119-29.
32. Swoboda I, Bugajska-Schretter A, Linhart B, Verdino P, Keller W, Schulmeister U, et al. A recombinant hypoallergenic parvalbumin mutant for immunotherapy of IgE-mediated fish allergy. J Immunol. 2007;178(10):6290-6.
Published
2020-06-23
How to Cite
1.
Mohammadi M, Khamisipour G, Soltanpour F, Omrani F, Taheri B, Momenzadeh N, Fouladvand M. Rational Design of Hypoallergenic Vaccines: Blocking IgE-binding to Polcalcin Using Allergen-specific IgG Antibodies. Iran J Allergy Asthma Immunol. 19(3):276-288.
Section
Original Article(s)