Ghasemi, A and Falak, R and Mohammadi, M and Maleki, S.J and Assarezadegan, M.-A and Jafary, M (2020) Incorporation of T-cell epitopes from tetanus and diphtheria toxoids into in-silico-designed hypoallergenic vaccine may enhance the protective immune response against allergens. Iranian Journal of Basic Medical Sciences, 23 (5). pp. 636-644. ISSN 20083866
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Abstract
Objective(s): New generation of allergy vaccines is capable of promoting the development of protective IgG and blocking the functionality of allergen-specific IgE. We incorporated universal and powerful T-cell epitopes from tetanus and diphtheria toxoids (TD epitope) into recombinant Che a 2, the well-known allergic profilin of Chenopodium album, to determine its immunological properties. Materials and Methods: The sequence and accordingly the structure of the recombinant Che a 2 was altered to generate a hypoallergenic variant (rChe a 2.rs). Moreover, TD epitope was incorporated to produce a novel vaccine that was nominated as rChe a 2.rsT.D. The effect of treatment with these variants was evaluated on the generation of allergen-specific IgG class, as well as lymphocyte proliferation in mice. Moreover, IgE-binding characteristics of the allergic patients' sera were determined by ELISA and proliferation and cytokine production was measured in T-cells. Results: ELISA and dot blot revealed strong reduction of the IgE-reactivity of human sera to the variants of Che a 2 as compared to the wild-type molecule. Furthermore, Che a 2.rs and Che a 2.rsT.D induced much lower levels of IL5 and IL13 secretion from allergic patients' PBMCs in comparison to wild-type Che a 2 protein. In mice, rChe a 2.rsT.D induced high titers of Che a 2-specific IgG antibody capable of blocking IgE-binding to rChe a 2 and induced lymphocyte proliferation more potently than rChe a 2.rs. Conclusion: Collectively, incorporation of T-cell epitopes of tetanus and diphtheria into hypoallergenic vaccines can dramatically enhance anti-allergic immune mechanisms, particularly in poor responders.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Allergen Chenopodium album Diphtheria-tetanus vaccine Epitope T lymphocyte |
| Subjects: | Q Science > QR Microbiology > QR180 Immunology |
| Divisions: | Research Center > Persian Gulf Marine Biotechnology Research Center |
| Depositing User: | خدیجه شبانکاره |
| Date Deposited: | 20 Dec 2020 09:01 |
| Last Modified: | 20 Dec 2020 09:01 |
| URI: | http://eprints.bpums.ac.ir/id/eprint/9021 |
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