IMMUNOLOGY - Roitt I. - Mir 2000

Chapter 19. Vaccination

ADJUVANTS

In the 1920s, during The Development of heterologous sera for treating human infectious diseases, it was discovered that certain substances—specifically aluminum salts added to or emulsified in an antigen solution—substantially enhance antibody production, acting as adjuvants. (Aluminum hydroxide is still widely used, for example, in Vaccines containing diphtheria and tetanus toxoids.) Later, drawing on modern understanding of lymphocyte activation mechanisms and immunological memory formation, many researchers sought to develop improved adjuvants, particularly those capable of boosting T-Cell responses. While these novel adjuvants are listed in Fig. 19.16, it must be emphasized that none of them have yet been approved for routine human vaccination.

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Fig. 19.16. A wide variety of exogenous and endogenous substances can act as immunoadjuvants; however, only aluminum and calcium salts, along with whole-cell killed pertussis vaccine, are currently used as adjuvants in routine population vaccination.

Adjuvants either retain the antigen at the injection site or induce cytokine production

The impact of adjuvants on the Immune Response is generally thought to stem from two primary activities: their ability to retain (or even accumulate) the antigen at the site where it is exposed to lymphocytes (the "depot" effect), and their capacity to trigger the synthesis of cytokines that regulate lymphocyte Functions. Aluminum salts likely act mainly as a depot by inducing small granulomas where they remain trapped along with the adsorbed antigen. Next-generation adjuvants, such as Liposomes and immunostimulating complexes (ISCOMs), achieve a similar goal by delivering the entrapped antigen directly to antigen-presenting Cells. Bacterial-derived adjuvants—such as mycobacterial cell walls, endotoxins, and others—probably function primarily by stimulating The production of relevant cytokines. This hypothesis is supported by the fact that cytokines act as potent adjuvants, especially when linked directly to the antigen. The Use of cytokines is particularly valuable for vaccinating immunocompromised individuals (see Fig. 19.18), for whom standard vaccines are often ineffective. Furthermore, it is hoped that utilizing cytokines will allow researchers to steer the immune response in a desired direction—for instance, when polarization toward exclusively Th1 or Th2 memory cells is desired.