Advertisement

Food Science and Biotechnology

, Volume 23, Issue 1, pp 239–245 | Cite as

Development of an oral immunoadjuvant from cheonggukjang that is efficacious for both mucosal and systemic immunity

  • Inkyu Hwang
  • Daewoon Choi
  • Hyejeong See
  • Seong-Il Lim
  • Wonyong Kim
  • In Sik Chung
  • Dong-Hwa Shon
Research Article

Abstract

Immunological properties of a 50% ethanol/aqueous extract of cheonggukjang (CGJ), a fermented soybean product, were investigated as a potent, orallyavailable, and cost-effective immunoadjuvant. Different from cholera toxin, a widely used experimental oral adjuvant with effects limited to mucosal immunity in the gut, oraladministration of the CGJ extract had positive effects on both mucosal and systemic immunity. Administration of keyhole limpet hemocyanin (KLH) with the CGJ extract resulted in hyper-production of KLH-specific IgA in the gut and KLH-specific IgG in the serum. Oral-administration of the CGJ extract resulted in promotion of both Th1 and Th2 immune responses, thus eliminating concerns over an imbalanced Th1 and Th2 immune bias that is often observed upon administration of other commonly used immunoadjuvants. Ethanol/aqueous extraction of CGJ resulted in enrichment of polyphenolic compounds, including flavonoids, providing a potential extra health benefit.

Keywords

cheonggukjang oral vaccine mucosal immunity adjuvant fermented food 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Birt DF, Hendrich S, Wang W. Dietary agents in cancer prevention: Flavonoids and isoflavonoids. Pharmacol. Therapeut. 90:157–177 (2001)CrossRefGoogle Scholar
  2. 2.
    Gardner EM, Beli E, Clinthorne JF, Duriancik DM. Energy intake and response to infection with influenza. Annu. Rev. Nutr. 31:353–367 (2011)CrossRefGoogle Scholar
  3. 3.
    Aguilar JC, Rodriguez EG. Vaccine adjuvants revisited. Vaccine 25:3752–3762 (2007)CrossRefGoogle Scholar
  4. 4.
    Buonaguro L, Pulendran, B. Immunogenomics and systems biology of vaccines. Immunol. Rev. 239:197–208 (2011)CrossRefGoogle Scholar
  5. 5.
    Baylor NW, Egan W, Richman P. Aluminum salts in vaccines—US perspective. Vaccine 20:S18–S23 (2002)CrossRefGoogle Scholar
  6. 6.
    Behboudi S, Morein B, Villacres-Eriksson M. In vitro activation of antigen-presenting cells (APC) by defined composition of Quillaja saponaria Molina triterpenoids. Clin. Exp. Immunol. 105:26–30 (1996)CrossRefGoogle Scholar
  7. 7.
    Cluff CW. Monophosphoryl lipid A (MPL) as an adjuvant for anticancer vaccines: Clinical results. Adv. Exp. Med. Biol. 667:111–123 (2009)CrossRefGoogle Scholar
  8. 8.
    Hwang I, Choi D, See H, Kim W, Chung IS, Shon D. Beneficial effects of the mixed adjuvant of CpG plus monophosphoryl lipid A in immunization with a recombinant protein vaccine for hepatitis A. J. Korean Soc. Appl. Biol. Chem. 56:95–98 (2013)CrossRefGoogle Scholar
  9. 9.
    Veldhoen M, Brucklacher-Waldert V. Dietary influences on intestinal immunity. Nature Rev. Immunol. 12:696–708 (2012)CrossRefGoogle Scholar
  10. 10.
    Chiang SS, Pan TM. Beneficial effects of Lactobacillus paracasei subsp. paracasei NTU 101 and its fermented products. Appl. Microbiol. Biot. 93:903–916 (2012)CrossRefGoogle Scholar
  11. 11.
    Masood MI, Qadir MI, Shirazi JH, Khan IU. Beneficial effects of lactic acid bacteria on human beings. Crit. Rev. Microbiol. 37:91–98 (2011)CrossRefGoogle Scholar
  12. 12.
    Shih I, Van Y. The production of poly-(γ-glutamic acid) from microorganisms and its various applications. Bioresource Technol. 79:207–225 (2011)CrossRefGoogle Scholar
  13. 13.
    Xu Q, Yajima T, Li W, Saito K, Ohshima Y, Yoshikai Y. Levan (beta-2, 6-fructan), a major fraction of fermented soybean mucilage, displays immunostimulating properties via Toll-like receptor 4 signalling: induction of interleukin-12 production and suppression of T-helper type 2 response and immunoglobulin E production. Clin. Exp. Allergy 36:94–101 (2006)CrossRefGoogle Scholar
  14. 14.
    Hoggart A, Hoggart J, Honerlaw M, Pelus LM. A spoonful of sugar helps the medicine go down: a novel technique to improve oral gavage in mice. J. Am. Assoc. Lab. Anim. Sci. 49:329–334 (2010)Google Scholar
  15. 15.
    Kim S, Yang JY, Lee K, Oh KH, Gi M, Kim JM, Paik DJ, Hong S, Youn J. Bacillus subtilis-specific poly-gamma-glutamic acid regulates development pathways of naive CD4(+) T cells through antigen-presenting cell-dependent and -independent mechanisms. Int. Immunol. 21:977–990 (2009)CrossRefGoogle Scholar
  16. 16.
    Moon HJ, Lee JS, Talactac MR, Chowdhury MY, Kim JH, Park ME, Choi YK, Sung MH, Kim CJ. Mucosal immunization with recombinant influenza hemagglutinin protein and poly gammaglutamate/chitosan nanoparticles induces protection against highly pathogenic influenza A virus. Vet. Microbiol. 160:277–289 (2012)CrossRefGoogle Scholar
  17. 17.
    Uto T, Akagi T, Yoshinaga K, Toyama M, Akashi M, Baba M. The induction of innate and adaptive immunity by biodegradable poly(gamma-glutamic acid) nanoparticles via a TLR4 and MyD88 signaling pathway. Biomaterials 32:5206–5212 (2011)CrossRefGoogle Scholar
  18. 18.
    Singh A, Holvoet S, Mercenier A. Dietary polyphenols in the prevention and treatment of allergic diseases. Clin. Exp. Allergy 41:1346–1359 (2011)CrossRefGoogle Scholar
  19. 19.
    Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 65:55–63 (1983)CrossRefGoogle Scholar
  20. 20.
    Lequin R. Enzyme immunoassay (EIA)/enzyme-linked immunosorbance assay (ELISA). Clin. Chem. 51:2415–2418 (2005)CrossRefGoogle Scholar
  21. 21.
    George S, Brat P, Alter P, Amiot MJ. Rapid determination of polyphenols and vitamin C in plant-derived products. J. Agr. Food. Chem. 53:1370–1373 (2005)CrossRefGoogle Scholar
  22. 22.
    Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scanvenging effects on superoxide radicals. Food Chem. 64:555–559 (1999)CrossRefGoogle Scholar
  23. 23.
    Korea Food and Drug Administration. Available from: http://www.kfda.go.kr/eng/index.do?nMenuCode=27.
  24. 24.
    Datta SK, Sabet M, Nguyen KP, Valdez PA, Gonzalez-Navajas JM, Islam S, Mihajlov I, Fierer J, Insel PA, Webster NJ, Guiney DG, Raz E. Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax. P. Natl. Acad. Sci. USA 107:10638–10643 (2010)CrossRefGoogle Scholar
  25. 25.
    Brenchley JM, Douek DC. HIV infection and the gastrointestinal immune system. Mucosal Immunol. 1:23–30 (2008)CrossRefGoogle Scholar
  26. 26.
    Annane D, Bellissant E, Cavaillon J. Septic shock. Lancet 365:63–78 (2005)CrossRefGoogle Scholar
  27. 27.
    Nguyen TH, Casale TB. Immune modulation for treatment of allergic disease. Immunol. Rev. 242:258–271 (2001)CrossRefGoogle Scholar
  28. 28.
    O’Garra A, Murphy KM. From IL-10 to IL-12: How pathogens and their products stimulate APCs to induce T(H)1 development. Nat. Immunol. 10:929–932 (2009)CrossRefGoogle Scholar
  29. 29.
    Marrack P, McKee AS, Munks MW. Towards an understanding of the adjuvant action of aluminium. Nat. Rev. Immunol. 9:287–293 (2009)CrossRefGoogle Scholar
  30. 30.
    Spellberg B, Edwards JE Jr. Type 1/Type 2 immunity in infectious diseases. Clin. Infect. Dis. 32:76–102 (2001)CrossRefGoogle Scholar
  31. 31.
    Williams CM, Rahman S, Hubeau C, Ma HL. Cytokine pathways in allergic disease. Toxicol. Pathol. 40:205–215 (2012)CrossRefGoogle Scholar
  32. 32.
    Miossec P, van den Berg W. Th1/Th2 cytokine balance in arthritis. Arthritis Rheum. 40:2105–2115 (1997)CrossRefGoogle Scholar
  33. 33.
    Geller SE, Studee L. Soy and red clover for mid-life and aging. Climacteric. 9:245–263 (2006)CrossRefGoogle Scholar
  34. 34.
    Monk JM, Hou TY, Chapkin RS. Recent advances in the field of nutritional immunology. Exp. Rev. Clin. Immunol. 7:747–749 (2011)CrossRefGoogle Scholar

Copyright information

© The Korean Society of Food Science and Technology and Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Inkyu Hwang
    • 1
    • 2
  • Daewoon Choi
    • 1
  • Hyejeong See
    • 1
  • Seong-Il Lim
    • 1
  • Wonyong Kim
    • 3
  • In Sik Chung
    • 4
  • Dong-Hwa Shon
    • 1
  1. 1.Korea Food Research InstituteGyeonggiKorea
  2. 2.College of PharmacyChungnam National UniversityDaejeonKorea
  3. 3.Department of Microbiology, College of MedicineChuang-Ang UniversitySeoulKorea
  4. 4.Department of Genetic Engineering and Graduate School of BiotechnologyKyung-Hee UniversityGyeonggiKorea

Personalised recommendations