Targeting Proteins to Antigen-Presenting Cells and Induction of Cytokines as a Basis for Adjuvant Activity

  • Anthony C. Allison
  • Noelene E. Byars
Part of the NATO ASI Series book series (NSSA, volume 238)


The need for improved and new vaccines is evident. While live virus vaccines have been very useful, they can produce severed infections in persons whose immune systems are compromised because of congenital deficiency, malnutrition or infections (notably HIV). If subunit antigens can elicit equivalent protection they are preferred. Preparation of antigens by recombinant technology has opened up the possibility of a new generation of vaccines, but a safe and efficacious adjuvant is a necessary component. The only adjuvant approved for human use is aluminum hydroxide or phosphate. While alum is an effective adjuvant for bacterial toxoids it has limited efficacy in other situations, for reasons that will be discussed below.


Simian Immunodeficiency Virus Genital Herpes Adjuvant Arthritis Adjuvant Activity IgG2a Antibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allison, A. C, and Byars, N. E., 1986, An adjuvant formulation that selectively elicits the formation of antibodies of protective isotypes and cell-mediated immunity, J. Immun. Methods, 95:157.CrossRefGoogle Scholar
  2. Arden, N. H., Patriarca, P. A., and Kendal, A. P., 1986, Experiences in the use and efficacy of influenza vaccine in nursing homes, in: “Options for Control of Influenza”, A. P. Kendal, and P. A. Patriarca, eds., Alan R. Liss, New York.Google Scholar
  3. Berman, P. W., Gregory, T., Crase, P., and Laswky, L. A., 1985, Protection from genital herpes simplex type 2 infection with cloned glycoprotein D., Science, 227:1490.PubMedCrossRefGoogle Scholar
  4. Bomford, R., 1989, Aluminium salts: perspectives in their use as adjuvants, in: “Immunological Adjuvants and Vaccines”, G. Gregoriadis, A. C. Allison and G. Poste, eds., Plenum Press, London.Google Scholar
  5. Braemer, A., Peterson, M., Renneke, G., Bass, E., Allison, A. C, Byars, N. E., and Fraser, D., 1984, Effect of inactivated FeLV vaccines on the development of persistent viremia, Proc. 65th Conf. Res. Workers in Animal diseases (E.M. Kohler) (p. 10).Google Scholar
  6. Byars, N. E., and Allison, A. C, 1987, Adjuvant formulation for use in vaccines to elicit both cell-mediated and humoral immunity, Vaccine, 5:223.PubMedCrossRefGoogle Scholar
  7. Byars, N. E., Allison, A. C, Harmon, M. W., and Kendal, A. P., 1990, Enhancement of antibody responses to influenza B virus hemagglutinin by use of a new adjuvant formulation, Vaccine, 8:49.PubMedCrossRefGoogle Scholar
  8. Byars, N. E., Nakano, G., Welch, M., Lehman, D., and Allison, A. C, 1991, Improvement of Hepatitis B vaccine by the use of a new adjuvant, Vaccine, 9:309.PubMedCrossRefGoogle Scholar
  9. Campbell, M. J., Esserman, L., Byars, N. E., Allison, A. C, and Levy, R., 1989, Development of a new therapeutic approach to B-cell malignancy. The induction of immunity by the host against cell surface receptor on the tumour, Int. Rev. Immun., 4:251.CrossRefGoogle Scholar
  10. Ellouz, F., Adam, A., Ciorbaru, R., and Lederer, E., 1974, Minimal structural requirements for adjuvant activity of bacterial peptidoglycans, Biochem. Biophys, Res. Commun., 59:1317.CrossRefGoogle Scholar
  11. Fermandijian, S., Perly, B., Level, M., and Lefrancier, P., 1987, A comparative 1H-n.m.r. study of Mur and Ac-L-Ala-D-iGln (MDP) and its analogue murabutide: evidence for a structure involving two successive beta-turns in MDP, Carbohydr. Res., 16:23.CrossRefGoogle Scholar
  12. Finkelman, F. D., Holmes, J., Katona, I. M., Urban, J. F. Jr., Beckmann, M. P., Park, L. S., Schooley, K. A., Coffman, R. L., Mbsmann, T. R., and Paul, W. E., 1990, Lymphokine control of in vivo immunoglobulin isotype selection, Annu. Rev. Immunol., 8:303.PubMedCrossRefGoogle Scholar
  13. Fraser-Smith, E. B., Waters, R. V. and Matthews, T. R., 1982, Correlation between in vivo anti-Pseudomonas and anti-Candida activities and clearance of carbon by the reticuloendothelial system for various muramyl dipeptide analogs, using normal and immunosuppressed mice, Infect. Immun., 35:105.PubMedGoogle Scholar
  14. Geczy, A. F., Alexander, K., Bashir, H. V., Edmonds, J. P., Uipfold, L., and Sullivan, J., 1983, HLA-B27, Klebsiella and ankylosing spondylitis: biological and chemical studies, Immun. Rev., 70:23.PubMedCrossRefGoogle Scholar
  15. Girard, M., Kieny, M.-P. and Pinter, A., 1991, Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus, Proc. Natl. Acad. Sci. USA, 88:542.PubMedCrossRefGoogle Scholar
  16. Gosselin, R. E., Hodge, H. C., Smith, R. P. and Gleason, M. N., 1976, “Clinical toxicology of commercial products,” Fourth Edition, Williams & Wilkins Company, Baltimore.Google Scholar
  17. Hayward, A. R., Burger, R., Scheper, R. and Arvin, A. M., 1991, Major. histocompatibility complex restriction of T-cell responses to varicella-zoster virus in guinea pigs, J. Virol., 65:1491.PubMedGoogle Scholar
  18. Hunter, R. L., Strickland, F. and Kezdy, F., 1981, The adjuvant activity of nonionic block polymer surfactants. I. The role of hydrophile-lipophile balance, J. Immun., 127:1244.PubMedGoogle Scholar
  19. Jones, W. R., Bradley, J., Judd, S. J., Denholm, E. H., Ing, R. M. Y., Mueller, U. W., Powell, J., Griffin, P. W. and Stevens, V. C, 1988, Phase I clinical trials of a World Health organization birth control vaccine, Lancet, i:1295.CrossRefGoogle Scholar
  20. Kaminski, M. S., Kitamura, K., Maloney, D. G., Campbell, M. J. and Levy, R., 1986, Importance of antibody isotype in monoclonal antiidiotype therapy of murine B cell lymphoma. A study of hybridoma class-switch variants, J. Immunol., 136:1123.PubMedGoogle Scholar
  21. Kenney, J. S., Hughes, B. W., Masada, M. P. and Allison, A. C, 1989, Influence of adjuvants on the quantity, affinity, isotype and epitope specificity of murine antibodies, J. Immun. Methods, 121:157.CrossRefGoogle Scholar
  22. MacLennan, I., 1991, The centre of hypermutation, Nature, 354:352.PubMedCrossRefGoogle Scholar
  23. Marx, P. A., Pedersen, N. C, Lerche, N. W., Osborn, K. G., Lowenstine, L. J., Lackner, A. A., Maul, D. H., Kwang, H.-S., Kluge, J. D., Zaiss, C. P., Sharpe, V., Spinner, A. P., Allison, A. C. and Gardner, M. B., 1986, Prevention of simian acquired immunodeficiency syndrome with a formalin-inactivated Type D retrovirus vaccine, J. Virol., 60:431.PubMedGoogle Scholar
  24. Metlay, J. P., Pure, E. and Steinman, R. M., 1990, Control of immune response at the level of antigen-presenting cells: a comparison of the function of dendritic cells and B-lymphocyctes, Adv. Immunol., 47:45.CrossRefGoogle Scholar
  25. Morgan, A. J., Allison, A. C, Finerty, S., Scullion, F. T., Byars, N. E., and Epstein, M. A., 1989, Validation of a first generation Epstein-Barr virus vaccine preparation suitable for human use, J. Mad. Virol., 29:74.CrossRefGoogle Scholar
  26. Morris, A. G., Lin, Y.-L. and Askonas, B. A., 1982, Immune interferon release when a cloned cytotoxic T-cell line meets its correct influenza-infected target, Nature, 295:150.PubMedCrossRefGoogle Scholar
  27. Mosmann, T. R. and Coffman, R. L., 1989, TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties, Annu. Rev. Immunol., 7:145.PubMedCrossRefGoogle Scholar
  28. Murray, R., Cohen, P. and Hardegree, M. C, 1972, Mineral oil adjuvants: biological and chemical studies, Ann. Allergy, 30:146.PubMedGoogle Scholar
  29. Murphey-Corb, M., Martin, L. N., Davison-Fairburn, B., Okawa, S., Baskin, G. B., Zhang, J.-Y., Mbntelaro, R. C, Miller, M., West, M., Allison, A. C. and Eppstein, D. A., 1989, A formalin inactivated whole simian immunodeficiency virus vaccine confers protection in macaques, Science, 246:1293.PubMedCrossRefGoogle Scholar
  30. Nagao, S. and Tanaka, A., 1980, Muramyl dipeptide-induced adjuvant arthritis, Infect. Immun., 28:624.PubMedGoogle Scholar
  31. Nicholson, K. G., Tyrrell, D. A. J., Harrison, P., Potter, C. W., Jennings, R., Clark, A., Schild, G. C, Wood, J. M., Yells, R., Seagrott, V., Huggens, A. and Anderson, S. G., 1979, Clinical studies of monovalent inactivated whole virus and subunit A/USSR/77 (H1N1) vaccine: serological and clinical reactions, J. Biol. Stand., 7:123.PubMedCrossRefGoogle Scholar
  32. Potter, M. and Boyce, C. R., 1972, Induction of plasma cell neoplasms in BALB/c strain mice with mineral oil and mineral oil adjuvants, Nature, 193:1086.CrossRefGoogle Scholar
  33. Reichmann, L., Clark, M., Waldmann, H. and Winter, G., 1988, Reshaping human antibodies for therapy, Nature, 332:323.CrossRefGoogle Scholar
  34. Ribi, E., Ulrich, J. T. and Masihi, K. N., 1987, Immunopotentiating activities of monophosphoryl lipid A, in: “Immunopharmacology of Infectious Diseases: Vaccine Adjuvants and Modulators of Nonspecific Resistance,” J. A. Majde, ed., Alan R. Liss, New York.Google Scholar
  35. Rickinson, A. B., Rowe, M., Hart, I. J., Yao, W. Y., Henderson, L. E., Robin, H. and Epstein, M. A., 1984, T cell-mediated regression of “spontaneous” and of Epstein-Barr virus-induced B-cell transformation in vitro: studies with cyclosporin A, Cell. Immunol, 87:646.PubMedCrossRefGoogle Scholar
  36. Steplewski, Z., Spira, G., Blasczyc, M., Lusbeck, M. D., Radlmuch, A., Illges, H., Herlyn, D., Rajewsky, K. and Scharff, M., 1985, Isolation and characterization of anti-monosialoganglioside monoclonal antibody 19-9S class switch variants, Proc. Natl, Acad, Sci. USA, 82:3653.CrossRefGoogle Scholar
  37. Takahashi, H., Takeshita, T., Morein, B., Putney, S., Germain, R. N. and Berzofsky, J. A., 1990, Induction of CD8+ cytotoxic T-cells by immunization with purified HIV-1 envelope protein in ISCOMS, Nature, 344:873.PubMedCrossRefGoogle Scholar
  38. Tew, J. G., Kosco, M. H. and Szakal, A. K., 1989, The alternative antigen pathway, Immunol. Today, 10:229.PubMedCrossRefGoogle Scholar
  39. Unkeless, J. C. Scaling, E. and Freedman, V. H., 1988, Structure and function of human and murine receptors for IgG, Ann. Rev. Immun., 6:251.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Anthony C. Allison
    • 1
  • Noelene E. Byars
    • 1
  1. 1.Institute of Immunology and Biological Sciences, Syntex ResearchPalo AltoUSA

Personalised recommendations