Choice and Design of Adjuvants for Parenteral and Mucosal Vaccines.
The existence of pathogens that escape recognition by specific vaccines, the need to improve existing vaccines and the increased availability of therapeutic (non-infectious disease) vaccines necessitate the rational development of novel vaccine concepts based on the induction of protective cell-mediated immune responses. For naive T-cell activation, several signals resulting from innate and adaptive interactions need to be integrated, and adjuvants may interfere with some or all of these signals. Adjuvants, for example, are used to promote the immunogenicity of antigens in vaccines, by inducing a pro-inflammatory environment that enables the recruitment and promotion of the infiltration of phagocytic cells, particularly antigen-presenting cells (APC), to the injection site. Adjuvants can enhance antigen presentation, induce cytokine expression, activate APC and modulate more downstream adaptive immune reactions (vaccine delivery systems, facilitating immune Signal 1). In addition, adjuvants can act as immunopotentiators (facilitating Signals 2 and 3) exhibiting immune stimulatory effects during antigen presentation by inducing the expression of co-stimulatory molecules on APC. Together, these signals determine the strength of activation of specific T-cells, thereby also influencing the quality of the downstream T helper cytokine profiles and the differentiation of antigen-specific T helper populations (Signal 3). New adjuvants should also target specific (innate) immune cells in order to facilitate proper activation of downstream adaptive immune responses and homing (Signal 4). It is desirable that these adjuvants should be able to exert such responses in the context of mucosal administered vaccines. This review focuses on the understanding of the potential working mechanisms of the most well-known classes of adjuvants to be used effectively in vaccines.
Cell Biology and Immunology, Wageningen University, Wageningen, P.O. Box 338, 6700 AH Wageningen, The Netherlands. huub.savelkoul@wur.nl.
Huub F J
HF
Savelkoul
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK. v.a.ferro@strath.ac.uk.
Valerie A
VA
Ferro
Department of Immunology, Center of Oncosurgery, National Cancer Institute, P. Baublio Str. 3b-321, LT-08406 Vilnius, Lithuania. strioga@gmail.com.
Marius M
MM
Strioga
Cell Biology and Immunology, Wageningen University, Wageningen, P.O. Box 338, 6700 AH Wageningen, The Netherlands. schijns.virgil@gmail.com.|Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK. schijns.virgil@gmail.com.|ERC-Belgium and ERC-The Netherlands, 5374 RE Schaijk, The Netherlands. schijns.virgil@gmail.com.
Virgil E J C
VE
Schijns
adjuvant; immunology; mechanisms