To maximize the effectiveness of vaccines, especially those containing poorly antigenic components or highly purified antigens, it is standard procedure to add adjuvants to the vaccine. Adjuvants trigger innate immune responses that serve to enhance the adaptive response to vaccines and/or balance or shift the nature of these immune response in the direction of either type 1 or type 2 responses. They can reduce the dose of antigen to be injected or the number of doses administered, and they may prolong immunologic memory. Adjuvants work through the following four major mechanisms:
Depot adjuvants protect antigens from degradation and prolong immune responses as a result of the sustained release of antigen over a period of time. Examples of depot-forming adjuvants include oil in water emulsions.
Another form of adjuvants consists of particles that effectively deliver antigen to antigen-presenting dendritic cells and so enhance antigen presentation. The immune system traps and processes particles such as bacteria or other microorganisms much more efficiently than soluble antigens. As a result, particulate antigens are much more effective than soluble ones. Examples of such adjuvants include emulsions, microparticles, immune-stimulating complexes, and liposomes.
Some antigens trigger innate immune responses by simply causing tissue damage and inflammation. Aluminum-based adjuvants cause release of inflammatory molecules and cytokines and simply trigger innate immunity. Saponin-based adjuvants and water in oil emulsions also act by causing tissue damage. Saponins (triterpene glycosides) are detergent-like molecules derived from the bark of the soapbark tree (Quillaja saponaria). Saponin-based adjuvants may selectively stimulate TH1 activity.
The final form of adjuvant contains microbial products that often represent pathogen-associated molecular patterns that trigger innate immunity. As a result, they activate dendritic cells and macrophages through toll-like receptors and stimulate the secretion of critical cytokines such as IL-1 and IL-12. Depending on the specific microbial product used, they may enhance either TH1 or TH2 responses. Commonly used microbial immunostimulants include lipopolysaccharides (or their detoxified derivatives), killed anaerobic corynebacteria (especially Propionibacterium acnes), and killed Mycobacteria.
Many commercially available and proprietary adjuvants are combinations. For example, very effective adjuvants can be constructed by combining particulate or depot adjuvants with an immunostimulatory agent.