Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides.

Abstract

Mucosal delivery of peptide/protein therapeutics via the oral route is a desirable strategy in human immunotherapy. A key step for enhancing the bioavailability of orally administered therapeutics is to protect them from enzymatic digestion in the gastrointestinal tract. Here, we generated transgenic rice seeds accumulating allergen-derived T cell epitopes, a model tolerogen for the control of pollen allergy, in either ER-derived protein body-I (PB-I) or protein storage vacuole protein body-II (PB-II). Compared with PB-II-localized or chemically synthesized forms, PB-I-localized T cell epitopes showed higher resistance to enzymatic digestion in simulated gastric fluid. Moreover, the dose of T cell epitope required for suppression of allergen-specific IgE in mice was about 20-fold lower when fed in PB-I localized form than when unprotected. These findings demonstrate the potential of bioencapsulation in PB-I for broad applications as a viable strategy to achieve efficient mucosal delivery of oral peptide/protein therapeutics.

• Authors: Hidenori Takagi, Takachika Hiroi, Sakiko Hirose, Lijun Yang, Fumio Takaiwa
• Journal: Peptides (Peptides) Vol. 31 Issue 8 Pg. 1421-5 (Aug 2010) ISSN: 1873-5169 [Electronic] United States
• PMID: 20457197 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Plant
• Cry j I protein, Cryptomeria japonica
• Cry j II protein, Cryptomeria japonica
• Epitopes, T-Lymphocyte
• Peptides
• Plant Proteins
• Recombinant Fusion Proteins
• Immunoglobulin E

Topics

• Administration, Oral
• Animals
• Antigens, Plant (genetics, immunology)
• Cytoplasmic Vesicles (metabolism, ultrastructure)
• Dose-Response Relationship, Immunologic
• Drug Delivery Systems
• Endoplasmic Reticulum (metabolism)
• Epitopes, T-Lymphocyte (biosynthesis, genetics, immunology)
• Gastric Juice (metabolism)
• Hypersensitivity (prevention & control)
• Immunoglobulin E (blood, immunology)
• Immunosuppression Therapy
• Male
• Mice
• Mice, Inbred BALB C
• Oryza (genetics, metabolism)
• Peptides (administration & dosage, genetics, immunology, metabolism)
• Plant Proteins (administration & dosage, genetics, immunology, metabolism)
• Plants, Genetically Modified (metabolism)
• Pollen (immunology)
• Recombinant Fusion Proteins (administration & dosage, genetics, immunology, metabolism)
• Seeds (metabolism, ultrastructure)