MICROBIOLOGY NOTES

 

   
ADJUVANTS

Substances that can enhance the immune response to an immunogen (antigen) are called adjuvants. They are not antigenic by themselves and alone cannot initiate any immune response by themselves. Adjuvants have the capability of stimulating the rapid and sustained production of high titers of antibodies with high avidity and influencing some properties of cell-mediated immunity. The use of adjuvants is required for many antigens which by themselves are weakly immunogenic. 
The action of adjuvants include:

  • Enhance long-term release of the antigen by functioning as a depot. Slow release of antigen stimulates the immune system for long durations.
  • Increases the number of cells involved in immune response.
  • Adjuvants may act as non-specific mediators of immune cell function by stimulating or modulating immune cells.
  • Provides more efficient processing of antigen.
  • Adjuvants may also enhance macrophage phagocytosis after binding the antigen.
  • Increase the rate of synthesis and release of antibodies.
  • Stimulates the production of cytokines
Types of adjuvants:
  • Repository adjuvants: These include aluminum (aluminum hydroxide, aluminum phosphate) and calcium (calcium alginate) salts. The salts combine with antigen to form an insoluble complex that slows the release of antigen from the site of subcutaneous or intramuscular injection. It aggregates proteins to make them easier for phagocytes to engulf. Most frequently used as adjuvants for vaccine antigen delivery. Generally weaker adjuvants than emulsion adjuvants. Best used with strongly immunogenic antigens. Generally produce mild inflammatory reactions.

  • Water-in-oil emulsions: The emulsified adjuvant allows slow release of antigen from oil droplets. Since there is variety in droplet size, the droplets are degraded at different rates resulting in prolonged presence of antigen. Antigen in oil droplet are more easily phagocytosed than soluble antigen. Example: Freund's incomplete antigen. Incomplete Freund's adjuvant is used for the booster immunizations following the initial injection with antigen-CFA. May be used for initial injection if the antigen is strongly immunogenic. Freund's complete adjuvant (CFA) is Freund's incomplete adjuvant and 0.5 mg/ml of killed Mycobacteria. The paraffin oil is not metabolized; it is either expressed through the skin (via a granuloma or abscess) or phagocytized by macrophages. The Mycobacteria induce granuloma formation at the site of injection. The granuloma further slows the release of antigen because it is a physical barrier. The component of the mycobacteria responsible for the adjuvant effect is muramyl dipeptide, which probably act mainly by stimulating cytokine production. This is not recommended for use in humans because the granuloma may be disfiguring. Montanide Incomplete seppic adjuvant is a mineral oil adjuvant. Other water-in-oil adjuvant systems are Ribi Adjuvant System, TiterMax and Syntex Adjuvant Formulation.

  • Nitrocellulose-adsorbed antigen: The nitrocellulose is basically inert, leading to almost no inflammatory response. Slow degradation of nitrocellulose paper allows prolonged release of antigen. Does not produce as dramatic an antibody response as CFA.

  • Lipopolysaccharide (endotoxin): Endotoxins of gram negative bacteria may be used as adjuvant. These agents enhance the IgM response, the exact mechanism of which is not known. It is not recommended for human use because it induces fever.

  • Bordetella pertussis: This bacterium is another adjuvant that increases the amount of IgM produced. In addition, Bordetella can mobilize T and B cells to site of injection, thereby enhancing immune response.

  • Immune-stimulating complexes (ISCOMs) are antigen modified saponin/cholesterol micelles. Both cell-mediated and humoral immune responses are elicited and has low toxicity. They stimulate cellular immune responses by delivering antigen to the cytoplasm of antigen-presenting cells. Liposomes can also be used as they are based on similar principle.

  • BCG: Nonspecific immune stimulation of cancer patients with adjuvants such as BCG has been tried for many years. Typically, the adjuvant would be injected at the site of the tumor in hopes of activating macrophages and promoting macrophage-mediated tumor cell killing.

  • L-tyrosine: A co-precipitate of the amino acid and antigen has been shown to have excellent adjuvant properties, even surpassing Freund's complete adjuvant in some circumstances. 

Side-effects:  Many of the adjuvants have the capacity to cause inflammation, tissue necrosis and pain in animals. Adjuvants are known to be able to break tolerance to antigens including self antigens. They may also be responsible for production of "adjuvant diseases" such as allergic disseminated encephalomyelitis. Multiple exposures to CFA will cause severe hypersensitivity reactions.


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  Last edited in April 2024