Transgenic Research

, Volume 23, Issue 4, pp 573–584 | Cite as

Development of a rice-based peptide vaccine for Japanese cedar and cypress pollen allergies

Original Paper

Abstract

Peptide immunotherapy using dominant T-cell epitopes is a safe treatment alternative to conventional subcutaneous injection of natural crude allergen extract, which is sometimes accompanied by anaphylactic shock. For Japanese cedar pollinosis (JCP), hybrid peptides composed of six to seven major T-cell epitopes (7Crp peptide) from the causative allergens Cry j 1 and Cry j 2 have been developed on the basis of different human leukemia antigen class II restrictions, because of the diversity of patients’ genetic backgrounds. However, other dominant T-cell epitopes that are produced in some patients are not covered by these peptides. To develop a more universal peptide vaccine for JCP, we generated transgenic rice seeds containing seven new T-cell epitopes (Crp3) in addition to the T-cell epitopes used in the 7Crp peptide. Next, we co-expressed unique T-cell epitopes (6Chao) from the Japanese cypress pollen allergens Cha o 1 and Cha o 2 in transgenic rice seeds, with 7Crp and Crp3. These transgenic rice seeds, containing many highly homologous T-cell epitopes derived from cedar and cypress allergens, are expected to be applicable to a wide range of patients suffering from these pollen allergies.

Keywords

Allergy vaccine Oral vaccine Peptide immunotherapy Pollinosis Transgenic rice seeds 

Abbreviations

ER

Endoplasmic reticulum

GALT

Gut-associated lymphoid tissue

HLA

Human leukemia antigen

JCP

Japanese cedar pollinosis

PBMC

Peripheral blood mononuclear cells

PB

Protein body

2-MER

2-Mercaptoethanol

Notes

Acknowledgments

We thank Ms M. Utsuno, Y. Ikemoto, K. Miyashita, and Y. Yajima for technical assistance. This work was supported by a grant from the Agri-Health Translational Research Project grant from the Ministry of Agriculture Forestry and Fisheries of Japan.

Supplementary material

11248_2014_9790_MOESM1_ESM.docx (20 kb)
Supplementary material 1 (DOCX 20 kb)

References

  1. Baba K, Nakae K (2008) Epidemiology of nasal allergy through Japan. Prog Med 28:2001–2012 (in Japanese)Google Scholar
  2. Frew AJ (2010) Allergen immunotherapy. J Allergy Clin Immunol 125(Suppl 2):S306–S313PubMedCrossRefGoogle Scholar
  3. Goto F, Yoshihara T, Shigemoto N, Toki S, Takaiwa F (1999) Iron fortification of rice seed by the soybean ferritin gene. Nat Biotechnol 17:282–286PubMedCrossRefGoogle Scholar
  4. Hashiguchi S, Hino K, Taniguchi Y, Kurimoto M, Fukuda K, Ohyama M, Fujiyoshi T, Sonoda S, Nishimura Y, Yamada G, Sugimura K (1996) Immunodominance of seven regions of a major allergen, Cry j 2, of Japanese cedar pollen for T-cell immunity. Allergy 51:621–632PubMedCrossRefGoogle Scholar
  5. Hirahara K, Tatsuta T, Takatori T, Otsuka M, Kirinaka H, Kawaguchi J, Serizawa N, Taniguchi Y, Saito S, Sakaguchi M, Inouye S, Shiraishi A (2001) Preclinical evaluation of an immunotherapeutic peptide comprising 7 T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen allergens. J Allergy Clin Immunol 108:94–100PubMedCrossRefGoogle Scholar
  6. Holgate S, Polosa R (2008) Treatment strategies for allergy and asthma. Nat Rev Immunol 8:218–230PubMedCrossRefGoogle Scholar
  7. Komiyama N, Sone T, Shimizu K, Morikubo K, Kino K (1994) cDNA cloning and expression of Cry j II, the second major allergen of Japanese cedar pollen. Biochem Biophys Res Commun 201:1021–1028PubMedCrossRefGoogle Scholar
  8. Larche M (2007) Peptide immunotherapy for allergic diseases. Allergy 62:325–331PubMedCrossRefGoogle Scholar
  9. Larche M, Akdis CA, Valenta R (2006) Immunological mechanisms of allergen-specific immunotherapy. Nat Rev Immunol 6:761–771PubMedCrossRefGoogle Scholar
  10. Masuyama K, Chikamatsu K, Ikegawa S, Matsuoka T, Takahashi G, Yamamoto T, Endo S (2009) Analysis of helper T cell responses to Cry j 1-derived peptides in patients with nasal allergy: candidate for peptide-based immunotherapy of Japanese cedar pollinosis. Allergol Int 58:63–70PubMedCrossRefGoogle Scholar
  11. Mori T, Yokoyama M, Komiyama N, Okano M, Kino K (1999) Purification, identification, and cDNA cloning of Cha o 2, the second major allergen of Japanese cypress pollen. Biochem Biophys Res Commun 263:166–171PubMedCrossRefGoogle Scholar
  12. Namba M, Kurose M, Torigoe K, Hino K, Taniguchi Y, Fukuda S, Usui M, Kurimoto M (1994) Molecular cloning of the second major allergen, Cry j II, from Japanese cedar pollen. FEBS Lett 353:124–128PubMedCrossRefGoogle Scholar
  13. Oono N, Ide T, Sakaguchi M, Inouye S, Saito S (2000) Common antigenicity between Japanese cedar (Cryptomeria japonica) pollen and Japanese cypress (Chamaecyparis obtuse) pollen, II. Determination of the cross-reacting T-cell epitope of Cry j 1 and Cha o 1 in mice. Immunology 99:630–634CrossRefGoogle Scholar
  14. Qu LQ, Takaiwa F (2004) Tissue specific expression and quantitative potential evaluation of seed storage component gene promoters in transgenic rice. Plant Biotech J 2:113–125CrossRefGoogle Scholar
  15. Sone T, Komiyama N, Shimizu K, Kusakabe T, Morikubo K, Kino K (1994) Cloning and sequencing of cDNA coding for Cry j I, a major allergen of Japanese cedar pollen. Biochem Biophys Res Commun 199:619–625PubMedCrossRefGoogle Scholar
  16. Sone T, Morikubo K, Miyahara M, Komiyama N, Shimizu K, Tsunoo H, Kino K (1998) T cell epitopes in Japanese cedar (Cryptomeria japonica) pollen allergens: choice of major T cell epitopes in Cry j 1 and Cry j 2 toward design of the peptide-based immunotherapeutics for the management of Japanese cedar pollinosis. J Immunol 161:448–457PubMedGoogle Scholar
  17. Sone T, Dairiki K, Morikubo K, Shimizu K, Tsunoo H, Mori T, Kino K (2005) Identification of human T cell epitopes in Japanese cypress pollen allergen, Cha o 1, elucidates the intrinsic mechanism of cross allergenicity between Cha o 1 and Cry j 1, the major allergen of Japanese cedar pollen, at the T cell level. Clin Exp Allergy 35:664–671PubMedCrossRefGoogle Scholar
  18. Sone T, Dairiki K, Morikubo K, Shimizu K, Tsunoo H, Mori T, Kino K (2009) Recognition of T cell epitopes unique to Cha o 2, the major allergen in Japanese cypress pollen, in allergic patients cross-reactive to Japanese cedar and Japanese cypress pollen. Allergol Int 58:237–245PubMedCrossRefGoogle Scholar
  19. Suzuki M, Komiyama N, Ithoh M, Itoh H, Sone T, Kino K, Takagi I, Ohta N (1996) Purification, characterization and molecular cloning of Cha o 1, a major allergen of Chamaecyparis obtuse (Japanese cypress) pollen. Mol Immunol 33:451–460PubMedCrossRefGoogle Scholar
  20. Tada Y, Utsumi S, Takaiwa F (2003) Foreign gene products can be enhanced by introduction into low storage protein mutants. Plant Biotech J 1:411–422CrossRefGoogle Scholar
  21. Takagi H, Hiroi T, Yang L, Tada Y, Yuki Y, Takamura K, Ishimitsu R, Kawauchi H, Kiyono H, Takaiwa F (2005a) A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE response. Proc Natl Acad Sci USA 102:17525–17530PubMedCentralPubMedCrossRefGoogle Scholar
  22. Takagi H, Saito S, Yang L, Nagasaka S, Nishizawa N, Takaiwa F (2005b) Oral immunotherapy against a pollen allergy using seed-based peptide vaccine. Plant Biotech J 3:521–533CrossRefGoogle Scholar
  23. Takagi H, Hirose S, Yasuda H, Takaiwa F (2006) Biochemical safety evaluation of transgenic rice seeds expressing T cell epitopes of Japanese cedar pollen allergens. J Agric Food Chem 54:9901–9905Google Scholar
  24. Takagi H, Hiroi T, Hirose S, Yang L, Takaiwa F (2010) Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides. Peptides 31:1421–1425PubMedCrossRefGoogle Scholar
  25. Takaiwa F (2007) Transgenic rice seed as a nutriceutical delivery system. CAB Rev Perspect Agric Vet Sci Nutr Nat Resour 2:1–9Google Scholar
  26. Takaiwa F (2011) Seed-based oral vaccines as allergen-specific immunotherapies. Hum Vaccine 7:357–366CrossRefGoogle Scholar
  27. Takaiwa F (2013) Update on the use of transgenic rice seeds in oral immunotherapy. Immunotherapy 5:301–312PubMedCrossRefGoogle Scholar
  28. Takaiwa F, Hirose S, Takagi H, Yang L, Wakasa Y (2009) Deposition of a recombinant peptide in ER-derived protein bodies by retention with cysteine-rich prolamins in transgenic rice seed. Planta 229:1147–1158PubMedCrossRefGoogle Scholar
  29. Tsunematsu M, Yamaji T, Kozutsumi D, Murakami R, Kimura S, Kino K (2007) Effect of Cry-consensus peptide, novel recombinant peptide for immunotherapy of Japanese cedar pollinosis, on an experimental allergic thinitis model in B10.S mice. Allergol Int 56:465–472PubMedCrossRefGoogle Scholar
  30. Valenta R, Ferreira F, Focke-Tejkl N, Linhart B, Niederberger V, Swoboda I, Vrtala S (2010) From allergen genes to allergy vaccines. Ann Rev Immunol 28:211–241CrossRefGoogle Scholar
  31. Wakasa Y, Takaiwa F (2013) The use of rice seeds to produce human pharmaceuticals for oral therapy. Biotechnol J 8:1133–1143PubMedCrossRefGoogle Scholar
  32. Wakasa Y, Yasuda H, Takaiwa F (2006) High accumulation of bioactive peptide in transgenic rice seeds by expression of introduced multiple genes. Plant Biotech J 4:499–510Google Scholar
  33. Yamanaka K, Yuta A, Kaked M, Sasaki R, Kitagawa H, Gabazza E, Okubo K, Kurokawa I, Mizutani H (2009) Induction of IL-10-producing regulatory T cells with TCP diversity by epitope-specific immunotherapy in pollinosis. J Allergy Clin Immunol 124:842–845PubMedCrossRefGoogle Scholar
  34. Yang L, Hirose S, Takahashi H, Kawakatsu T, Takaiwa F (2012) Recombinant protein yield in rice seed is enhanced by specific suppression of endogenous seed proteins at the same deposit site. Plant Biotechnol J 10:1035–1045PubMedCrossRefGoogle Scholar
  35. Yasueda H, Saitou K, Sahashi N (2001) Relationship between pollen counts of Cryptomeria japonica and Cupressaceae and the severity of allergic symptoms. Allergol Int 50:133–142CrossRefGoogle Scholar
  36. Yoshitomi T, Hirahara K, Kawaguchi J, Serizawa N, Taniguchi Y, Saito S, Sakaguchi M, Inouye S, Shiraishi A (2002) Three T-cell determinants of Cry j 1 and Cry j2, the major Japanese cedar pollen antigens, retain their immunogenicity and tolerogenicity in a linked peptide. Immunology 107:517–522PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Functional Transgenic Crop Research UnitNational Institute of Agrobiological SciencesTsukubaJapan

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