Adjuvants innate immune responses

Pashine, A., Valiante, N.M., and Ulmer, J.B. (2005) Targeting the innate immune response with improved vaccine adjuvants. Nat. Med. 11(4 Suppl), S63-68. 

The recent elucidation of the immunomodulatory activities of host defense peptides is perhaps the most intriguing to the development of these molecules as therapeutics. Importantly, many peptides that have been demonstrated to be devoid of antimicrobial activity under physiological conditions have maintenance of immunomodulatory activities. That host defense peptides have also recently been demonstrated to bridge innate and adaptive immune responses and as well act as adjuvants extends their therapeutic potential beyond the resolution of infection. Recent investigations have also sought to define the cell receptors involved in the immunomodulatory activities of host defense peptides in an effort to define the mechanism of action of these molecules and further the understanding of how these molecules are able to elicit such a broad range of... 

As stated above, the principal objective for the use of an adjuvant in a vaccine is to potentiate immune response to an Ag of minimal immunogenicity. How this potentiation is achieved varies from adjuvant to adjuvant and in many cases, the precise mechanism of ac tion is unknov n. However, as a rule, immune potentiation is accomplished by the ability of the adjuvant to induce a variety of non-specific activities within the innate arm of the immune system. Once activated, the innate branch of immunity, particularly the complement system, orchestrates the various humoral and cell-mediated responses that operate within and between the innate and acquired arms. The result is a generalized activation and potentiation of the immune system in response to the adjuvant with the hope that this generalized immune priming will allow for a more effective processing and recognition of the Ag contained within the vaccine. 

As described above, traditional adjuvants typically are derived from bacterial components in order to provide the bacteria signals necessary for the activation and potentiation of the innate arm of the immune system. One of the first components of innate immunity that becomes ac tivated in response to these bacterial signals is the complement system. 

---