Incorporation of T-cell epitopes from tetanus and diphtheria toxoids into in-silico-designed hypoallergenic vaccine may enhance the protective immune response against allergens.

Authors: GHASEMI, ALI - Semnan University Of Medical Sciences; FALAK, REZA - Iran University Of Medical Sciences; MOHAMMADI, MOHSEN - Bushehr Province University Of Medical Sciences; Maleki, Soheila; ASSAREZADEGAN, MOHAMMAD - Iran University Of Medical Sciences; JAFARY, MOJTABA - Bushehr Province University Of Medical Sciences

Submitted to: Iranian Journal of Basic Medical Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/30/2020
Publication Date: 5/1/2020
Citation: Ghasemi, A., Falak, R., Mohammadi, M., Maleki, S.J., Assarezadegan, M.A., 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. 23:636-644.

Interpretive Summary: A new generation of allergy vaccines is capable of promoting the development of protective immunoglobulin G (IgG) antibodies that are capable of blocking the functionality of allergen-specific immunoglobulin E (IgE). This new generation vaccine that can be used as a treatment against food allergy incorporated fragments of antigens known to stimulate strong immune responses (tetanus and diphtheria toxoid antigens) into a known allergen and a variant of this allergen. Upon injection of this engineered allergen into mice it was shown that the immune cell (T-cell and IgG) response was altered to a anti-allergic type of immune reaction. One major importance of this result is that it is likely to be effective in poor responders with weaker immune responses, like the elderly.

Technical 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 wellknown 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.