Immunological and Symptomatic Effects of Oral Intake of Transgenic Rice Containing 7 Linked Major T-Cell Epitopes from Japanese Cedar Pollen Allergens

Abstract

<b><i>Background:</i></b> A rice-based peptide vaccine containing 7 linked human predominant T-cell epitopes (7Crp) derived from Japanese cedar (JC) pollen allergens, Cry j 1 and Cry j 2, was developed. Here, we examined the efficacy and safety of this transgenic rice in JC pollinosis patients. <b><i>Methods:</i></b> Transgenic rice (5, 20, and 80 g) was administered orally. We measured the T-cell proliferative activity against 7Crp, Cry j 1, and Cry j 2; the cytokine expression levels; and specific IgE and IgG4 production levels. In addition, the symptom and medication scores were monitored during the pollen season, and quality of life (QOL) was evaluated. <b><i>Results:</i></b> T-cell proliferative activities to Cry j 1, Cry j 2, and 7Crp were significantly depressed in a dose-dependent manner. Oral intake of 80 g transgenic rice for 20 weeks resulted in significant suppression of allergen-specific T-cell proliferation with downregulation of IL-13 and upregulation of IL-10 levels but no changes to specific IgE and IgG4 levels. The QOL symptom scores for allergic rhinitis were not significantly improved. <b><i>Conclusions:</i></b> Allergen-specific T-cell responses were significantly reduced by oral intake of transgenic rice in a dose-dependent manner. However, neither medication score nor QOL symptom scores could be improved during the JC pollen season with oral intake of transgenic rice for 20 weeks.

Next-Generation Allergen-Specific Immunotherapy for Japanese Cedar Pollinosis Using Molecular Approaches

“…When the first clinical study of this transgenic rice in JC-pollinosis patients had been completed, it was found that allergen-specific T-cell proliferations against Cry j 1 and Cry j 2 allergens were significantly downregulated within just 2 weeks. 45 This suppressive effect was dose-dependent. On the other hand, when 80 g transgenic rice was orally administered for 20 weeks from December to the end of March, IL10 upregulation and IL13 downregulation were not associated with decreased cedar pollen–specific IgE antibodies or increased IgG 4 -blocking antibodies.…”

Contributions of the international plant science community to the fight against infectious diseases in humans—part 2: Affordable drugs in edible plants for endemic and re‐emerging diseases

“…The same principle has been used to produce recombinant allergy vaccines in rice seeds for allergen‐specific oral immunotherapy (Takaiwa et al ., 2015 ). A peptide vaccine‐containing seven linked human‐predominant T‐cell epitopes derived from Japanese cedar pollen allergens were also produced in rice (Saito et al ., 2020 ), and the efficacy and safety of the transgenic rice grains were confirmed after oral administration to JC pollinosis patients (Endo et al ., 2021 ).…”

Grains of Wisdom: Transgenic Rice for Oral Allergen Immunotherapy in Japanese Cedar Pollen-Allergic Patients

“…In conclusion, while allergen immunotherapy is still being explored by different mechanistic approaches, the study by Endo et al [1] supports a potential future for an effective and safer mucosal route of T-cell peptide immunotherapy with transgenic rice technology. Because of its potential impact on the improvement of quality of life in allergic disease, AIT will certainly stay a present and future therapy for respiratory and food allergies.…”

“…Allergen-specific immunotherapy (AIT) has been considered to date the only disease-modifying treatment in allergic rhinitis. In this issue of International Archives of Allergy and Immunology (IAAI), Endo et al [1] report the first use of transgenic rice to deliver high doses of allergen for oral immunotherapy of Japanese cedar allergic rhinitis patients. Vaccine development is among the greatest achievements in the history of medicine.…”

“…In this issue of IAAI, Endo et al [1] present a study on the T-cell peptide mucosal route of immunotherapy for cedar pollinosis patients. They used transgenic rice expressing 7 overlapping epitope T-cell peptides (7Crp) to deliver a high dose of allergen for specific T-cell tolerance induction.…”