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Freund's Adjuvants

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Vaccine Adjuvants

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 42))

Abstract

Freund’s adjuvants are water-in-mineral oil emulsions (W/O emulsions) without heat-killed mycobacteria added (Freund’s incomplete adjuvant) or with heat-killed mycobacteria added (Freund’s complete adjuvant). Freund’s adjuvants are, in a way, historic adjuvants and for many researchers the first and most obvious association to the word adjuvant at all. The adjuvants have been used extensively in experimental immunology owing to their high efficacy, and Freund’s incomplete adjuvant has been used for decades in practical veterinary vaccination. Vaccination of humans with Freund’s incomplete adjuvant was undertaken in the 1950s and was stopped because of adverse reactions in the mid-1960s.

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References

  1. Le Moignic and Pinoy (1916) Les vaccins en emulsion dans les corps gras ou “lipo-vaccins.” Comptes Rendus de la Societe de Biologie 79, 201–203.

    Google Scholar 

  2. Freund, J., Casals, J., and Hosmer, E. P. (1937) Sensitization and antibody formation after injection of tubercle bacili and paraffin oil. Proc. Soc. Exp. Biol. Med. 37, 509–513.

    CAS  Google Scholar 

  3. Freund, J. (1956) The mode of action of immunologic adjuvants, in Adv. Tuberc. Res. S. Karger, Basel, New York, pp. 130–148.

    Google Scholar 

  4. Raffel, S. (1948) The components of the tubercle bacillus responsible for the delayed type of “Infectious” allergy. J. Infect. Dis. 82, 267–293.

    Article  PubMed  CAS  Google Scholar 

  5. McKercher, P. D. and Graves, J. H. (1977) A review of the current status of oil adjuvants in foot-and-mouth disease vaccines. Dev. Biol. Stand. 35, 107–112.

    Google Scholar 

  6. Street, B. K. (1967) The use of an oil adjuvant equine influenza virus vaccine, in Symp.series immunobiol. Standard., vol. 6, Karger, Basel, New York, pp. 241–250.

    Google Scholar 

  7. Ott, G. L., Yaillen, A. J., and Korschak, J. (1962) Adjuvant killed hog cholera vaccine. Vet. Med. 57, 1060–1063.

    Google Scholar 

  8. Freund, J., Lipton, M. M., and Pisani, T. M. (1948) Immune response to rabies vaccine in water-in-oil emulsion. Proc. Soc. Exp. Biol. Med. 68, 609–610.

    PubMed  CAS  Google Scholar 

  9. McClelland, L., Hampil, B., Hamparian, V. V., Potash, L., Ketler, A., and Hilleman, M. R. (1961) Laboratory and field investigations of bovine myxovirus parainfluenza 3 virus and vaccine. II. Development and appraisal of potency of SF-4 (Shipping Fever) virus vaccine. J. Immunol. 87, 134–138.

    PubMed  CAS  Google Scholar 

  10. Eidson, C. S. (1982) Vaccination of breeder chickens and their progeny with a live or with an inactivated oil emulsion newcastle disease vaccine, in Develop. Biol. Stand. vol. 51, Karger, Basel, New York, pp. 191–205.

    Google Scholar 

  11. Fastier, L. B. and Hansen, N. F. (1964) An adjuvant vaccine against infectious canine hepatitis. New Z. Vet. J. 12, 89–91.

    Article  CAS  Google Scholar 

  12. Plowright, W., Herniman, K. A. J., Jessett, D. M., Kalunda, M., and Rampton, C. S. (1975) Immunization of cattle against the herpesvirus of malignant cattarrhal fever: failure of inactivated culture vaccines with adjuvant. Res. Vet. Set 19, 159–166.

    CAS  Google Scholar 

  13. Salk, J. E., Bailey, M. L., and Laurent, A. M. (1952) The use of adjuvants in studies on influenza immunization II. Increased antibody formation in human subjects inoculated with influenza virus vaccine in a water-in-oil emulsion. Amer. J. Hyg. 55, 439–456.

    PubMed  CAS  Google Scholar 

  14. Pittman, M. (1967) Some remarks regarding the reaction provoking properties, in Symp.series immunobiol. Standard., vol. 6, Karger, Basel, New York, pp. 101–102.

    Google Scholar 

  15. Salk, J. E., Benneth, B. L., Lewis, L. J., Ward, E. N., and Youngner, J. S. (1953) Studies in human subjects on active immunization against poliomyelitis. J. Am. Med. Assoc. 151, 1081–1098.

    PubMed  CAS  Google Scholar 

  16. Miller, L. F., Peckinpaugh, R. O., Arlander, T. R., Pierce, W. E., Edwards, E. A., De Berry, P., et al. (1965) Epidemiology and prevention of acute respiratory disease in naval recruits. II. Effect of adjuvant and aqueous adenovirus vaccines in prevention of naval recruit respiratory disease. Am. J. Publ. Health 55, 47–59.

    Article  CAS  Google Scholar 

  17. Woolridge, R. L., Grayston, J. T., Chang, I. H., Cheng, K. H., Yang, C. Y., and Neave, C. (1967) Field trial of a monovalent and bivalent mineral oil adjuvant trachoma vaccine in Taiwan school children. Am. J. Ophthalmol. 63, 1645.

    PubMed  Google Scholar 

  18. Cram, J. M. and Cram, D. J. (1978) Alkenes and alkynes, in The Essence of Organic Chemistry, Addison-Wesley, New York, pp. 77–97.

    Google Scholar 

  19. Friedewald, W. F. (1944) Adjuvants in immunization with influenza virus vaccines. J. Exp. Med. 80, 477–491.

    Article  PubMed  CAS  Google Scholar 

  20. Henle, W. and Henle, G. (1945) Effect of adjuvants on vaccination of human beings against influenza. Proc. Soc. Exp. Biol. N.Y. 59, 179–181.

    Google Scholar 

  21. Salk, J. E., Laurent, A. M., and Bailey, M. L. (1951) Direction of research on vaccination against influenza-new studies with immunologic adjuvants. Am. J. Publ. Health 41, 669–677.

    Article  CAS  Google Scholar 

  22. Salk, J. E. (1953) The use of adjuvants in studies on influenza immunization III. Degree of persistence of antibody in human subjects two years after vaccination. J. Am. Med. Assoc. 151, 1169–1175.

    Google Scholar 

  23. Tentative draft,minimum requirements for influenza vaccines emulsified in mineral oil.National Inst.of Health,1956,USA.

    Google Scholar 

  24. Dietz, W. A., King, W. H., Priestly, W., and Rehner, J. (1952) Properties of high boiling petroleum products. Ind. Eng. Chem. 44, 1818–1827.

    Article  CAS  Google Scholar 

  25. Freund, J., Thomson, K. J., Hough, H. B., Sommer, H. E., and Pisani, T. M. (1948) Antibody formation and sensitization with the aid of adjuvants. J. Immunol. 60, 383–398.

    PubMed  CAS  Google Scholar 

  26. Berlin, B. S. (1962) Tests for biological safety of Arlacel A. Ann. Allergy 20, 472–479.

    PubMed  CAS  Google Scholar 

  27. Herbert, W. J. (1967) Some investigations into the mode of action of the water-in-mineral-oil emulsion antigen adjuvants. Symp. Series Immunobiol. Standard., vol. 6, Karger, Basel, New York, pp. 213–220.

    Google Scholar 

  28. Wilner, B. I., Evers, M. A., Troutman, H. D., Trader, F. W., and McLean, I. W. (1963) Vaccine potentiation by emulsification with pure hydrocarbon compounds. J. Immunol. 91, 210–229.

    PubMed  CAS  Google Scholar 

  29. Stewart-Tull, D. E. S., Shimono, T., Kotani, S., and Knights, B. A. (1976) Immunosuppressive effect in mycobacterial adjuvant emulsions of mineral oils containing low molecular weight hydrocarbons. Int. Archs Allergy Appl. Immun. 52, 118–128.

    Article  Google Scholar 

  30. Shaw, C., Alvord, E. C., and Kies, M. W. (1964) Straight chain hydrocarbons as substitutes for the oil in Freund’s adjuvants in the production of experimental “allergic” encephalomyelitis in the guinea pig. J. Immunol. 92, 24–27.

    PubMed  CAS  Google Scholar 

  31. Freund, J. (1951) The effect of paraffin oil and mycobacteria on antibody formation and sensitization. A review. Am. J. Clin. Pathol. 21, 645–656.

    PubMed  CAS  Google Scholar 

  32. Stetten, D. (1943) Metabolism of paraffin. J. Biol. Chem. 147, 327–332.

    CAS  Google Scholar 

  33. Bollinger, J. N. (1970) Metabolic fate of mineral oil adjuvants using 14C-labeled tracers I: mineral oil. J. Pharm. Sci. 59, 1084–1088.

    Article  PubMed  CAS  Google Scholar 

  34. Bollinger, J. N. (1970) Metabolic fate of mineral oil adjuvants using 14C-labeled tracers II: mannide monooleate. J. Pharm. Sci. 59, 1088–1092.

    Article  PubMed  CAS  Google Scholar 

  35. Jollès, P. and Paraf, A. (1973) Biological activty of adjuvants, in Chemical and Biological Basis of Adjuvants (Kleinzeller, Springer, and Wittmann, eds.), Molecular Biol. Biochem. and Biophys. 13, 53–77.

    Google Scholar 

  36. Grun, J. L. and Maurer, P. H. (1989) Different T-helper cell subsets elicited in mice utilizing two different adjuvant vehicles: the role of endogenous interleukin-1 in proliferative responses. Cell. Immunol. 121, 134–145.

    Article  PubMed  CAS  Google Scholar 

  37. Lindblad, E. B., Elhay, M. E., Silva, R., Appelberg, R., and Andersen, P. (1997) Adjuvant modulation of the immune responses to tuberculosis subunit vaccines. Infect. Immun. 65, 623–629.

    PubMed  CAS  Google Scholar 

  38. Uede, T., Huff, T. F., and Ishizaka, K. (1982) Formation of IgE binding factors by rat T lymphocytes. V.: effect of adjuvant for the priming immunization on the nature of IgE binding factors formed by antigenic stimulation. J. Immunol. 129, 1384–1390.

    PubMed  CAS  Google Scholar 

  39. Uede, T. and Ishizaka, K. (1982) Formation of IgE binding factors by rat T lymphocytes. VI.: cellular mechanisms for the formation of IgE-potentiating factor and IgE-suppressive factor by antigenic stimulation of antigen primed spleen cells. J. Immunol. 129, 1391–1397.

    PubMed  CAS  Google Scholar 

  40. Smith, W. G. and Butchko, G. M. (1986) Regulation of in vivo IgE biosynthesis in mice with complete freund’s adjuvant. Int. Archs. Allergy Appl. Immun. 79, 337–342.

    Article  CAS  Google Scholar 

  41. Reinisch, C. L., Gleiner, N. A., and Schlossman, S. F. (1976) Adjuvant regulation of T cell function J. Immunol. 116, 710–715.

    PubMed  CAS  Google Scholar 

  42. Ke, Y., Li, Y., and Kapp, J. A. (1995) Ovalbumin injected with complete Freund’ s adjuvant stimulates cytotoxic responses. Eur. J. Immunol. 25, 549–553.

    Article  PubMed  CAS  Google Scholar 

  43. Kuzu, H., Kuzu, Y., Zaghouani, H., and Bona, C. (1993) In vivo priming effect during various stages of ontogeny of an influenza A virus nucleoprotein peptide. Eur. J. Immunol. 23, 1397–1400.

    Article  PubMed  CAS  Google Scholar 

  44. Valmori, D., Romero, J. F., Men, Y., Maryanski, J. L., Romero, P., and Corradin, G. (1994) Induction of a cytotoxic T cell response by co-injection of a T helper peptide and a cytotoxic T lymphocyte peptide in incomplete Freund’s adjuvant (IFA): further enhancement by preinjection of IFA alone. Eur. J. Immunol. 24, 1458–1462.

    Article  PubMed  CAS  Google Scholar 

  45. Wagner, R., Deml, L., Schirmbeck, R., Niedrig, M., Reimann, J., and Wolf, H. (1996) Construction, expression and immunogenicity of chimeric HIV-1 virus-like particles. Virology 220, 128–140.

    Article  PubMed  CAS  Google Scholar 

  46. Dvorak, A. M. and Dvorak, H. F. (1974) Structure of Freund’s complete and incomplete adjuvants. Immunology 27, 99–114.

    PubMed  CAS  Google Scholar 

  47. Chase, M. W. (1967) Production of antiserum, in Methods in Immunology and Immunochemistry (Williams, C. A. and Chase, M. W., eds.), vol. 1, Academic, New York, p. 197.

    Google Scholar 

  48. Stewart-Tull, D. E. S. (1996) The Use of Adjuvants in Experimental Medicine II. Water-in-Oil Emulsions, in Methods in Molecular Medicine: Vaccine Protocols (Robinson, A., Farrar, G., and Wiblin, C., eds.), Humana, Totowa, NJ.

    Google Scholar 

  49. Stewart-Tull, D. E. S. (1995) Freund-type mineral oil adjuvant emulsions, in The Theory and Practical Application of Adjuvants (Stewart-Tull, D. E. S., ed.), Wiley, New York, pp. 1–19.

    Google Scholar 

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Authors and Affiliations

  1. Superfos Biosector, Production, Frederikasund, Denmark

    Erik B. Lindblad

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  1. Erik B. Lindblad
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  1. Chiron Corporation, Emeryville, CA

    Derek T. O’Hagan

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© 2000 Humana Press Inc.

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Lindblad, E.B. (2000). Freund's Adjuvants. In: O’Hagan, D.T. (eds) Vaccine Adjuvants. Methods in Molecular Medicine™, vol 42. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-083-7:49

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  • DOI: https://doi.org/10.1385/1-59259-083-7:49

  • Publisher Name: Springer, Totowa, NJ

  • Print ISBN: 978-0-89603-735-9

  • Online ISBN: 978-1-59259-083-4

  • eBook Packages: Springer Protocols

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