Subunit vaccines of the future: the need for safe, customized and optimized particulate delivery systems.

A major challenge for current vaccine development is the fact that many new subunit vaccines based on highly purified recombinant proteins are poorly immunogenic and mobilize insufficient immune responses for protective immunity. Adjuvants are therefore needed in vaccine formulations to enhance, direct and maintain the immune response to vaccine antigens. Few adjuvants are currently approved for human use that mainly induce humoral immunity, and there is therefore an unmet medical need for development of effective and safe adjuvants that in addition can stimulate cellular or mucosal immunity, or combinations thereof, depending on the requirements for protection against the specific disease. Vaccine delivery systems are important components of adjuvants that allow proper delivery of antigens to antigen-presenting cells. Moreover, they often possess intrinsic immunopotentiating activity and/or can be customized towards a given immunological profile by the appropriate combination with immunopotentiating compounds. This article reviews the current status of human-tailored vaccine delivery with special focus on how to design safe particulate vaccine delivery systems with respect to composition, physicochemical properties, antigen association and choice of administration route, in order to better customize vaccine formulations towards specific diseases in the future.