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

• Main Authors: Mohsen Mohammadi, Gholamreza Khamisipour, Faezeh Soltanpour, Fatemeh Omrani, Behrooz Taheri, Niloofar Momenzadeh, Moradali Fouladvand
• Format: Article
• Language: English
• Published: Tehran University of Medical Sciences 2020-06-01
• Series: Iranian Journal of Allergy, Asthma and Immunology
• Subjects: Chenopodium album; Immunotherapy; Polcalcin; Recombinant fusion proteins; Vaccine
• Online Access: https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2552
• ISSN: 1735-1502; 1735-5249

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.