Vaccine adjuvants: Critical tools guiding vaccine-induced immune responses

Vaccine adjuvants are defined functionally as critical substances in vaccines that enhance adaptive immune responses to the antigen component within the vaccine (Ramon G, 1924). Prototype vaccine adjuvants have been classified functionally as facilitators of immune signal 1, i.e the delivery of antigen to antigen-specific lymphocytes (Jansen et al., 2005) or signal 2, i.e appropriate immunostimulation, in particular costimulation, during antigen recognition by lymphocyte receptors (Schijns, 2000). In addition, a third signal is needed to drive a selective T helper -cell type response, which enables activation of distinct adaptive defence pathways resulting in the proper immune effector elements. For example, the predominance of a Th1 type response, supporting the generation of CD8+ cytotoxic T lymphocytes (CTLs) is believed to be crucial for intracellular microorganisms and for tumor immunosurveillance (Driessens 2008). The nature of the third signal is highly dependent on the combination of vaccine adjuvant-induced signals, their duration and the order of delivery to antigen-presenting cells (APCs) (Kaiko 2008, Kalinski 1999, Macagno 2007). The generated fully functional effector T cells should reach the site of danger, i.e. the site of infection or tumor tissue, in order to execute their function. APCs are involved in determining the homing properties of effector T cells by providing signal 4, which includes the selective expression of appropriate chemokine receptors on the surface of effector T cells, e.g. CCR9 for their migration to gut (Mora 2005, Kim 2003). The ability of migratory DCs to control the homing potential of effector T cells depends on the type of DCs and the adjuvant-induced constellation of activation signals, triggered directly or via secondary mechanisms, in a particular anatomical location associated with the route of vaccine administration (Mora 2005).
Hence, the adjuvant provides a key ingredient in the vaccine to not only compensate for poor immunogenicity of refined, often recombinant, or synthetic vaccine antigen candidates, but also to evoke the desired type of immune effector response. Importantly, the selection of an inappropriate adjuvant may result in the activation of a non-protective immune pathway. While most traditional infectious disease vaccines are based on antibody responses (Bachmann and Zinkernagel 1997; Rappuoli 2007), for intracellular micro-organisms and for most malignancies, targeted by therapeutic immunization, Th1-type immune responses that are associated with cytotoxic T cells, are strongly implicated in protective immunity. Consequently, potential Th1 promoting vaccine adjuvants are being explored and tested.
Moreover, vaccine adjuvants not only improve the strength of an immune response, but can also accelerate its onset, and improve its duration, often leading to better memory. In case of expensive antigens or limited availability of antigens, adjuvants can help to reduce antigen dosing. In addition, adjuvants are capable of improving antigen stability. Importantly, as mentioned above, adjuvants can direct the immune response in the desired direction needed for protective immunity (Schijns, 2000; Schijns and Lavelle, 2011).
In the present issue various aspects, including theories, methods, areas of impact, historical aspect, etc., of a range of prototype and experimental vaccine adjuvants and their beneficial role in vaccine efficacy are highlighted.