Vaccine protocols for enhanced immunogenicity of exogenous antigens

Vaccination protocols aim at the delivery of exogenous antigen (Ag) to antigen-presenting cells (APCs) concurrent with the activation of APCs by adjuvants. Activated APCs then cross-present the Ag, cross-prime T effector cells, and activate B cells. Classical protocols rely on a mixture of both Ag and the adjuvant. However, a disadvantage of this strategy is that simultaneous “loading” and activation of APCs is not guaranteed. As a consequence, heterogeneous APC populations will be generated, including APCs being either Ag-presenting or only activated, thus rendering the adaptive immune response suboptimal. Therefore, novel strategies are needed that provide both constituents to the same APC in order to generate a homogeneous Ag-presenting and activated cell population. Here we show that these requirements can be fulfilled via two distinct methods, either by covalently linking Ag to the adjuvant or by co-encapsulating Ag and adjuvant into biodegradable microparticles. These novel vaccine protocols allow the generation of robust T-cell and B-cell responses that match immunogenicity of live vectors. Their characteristics with regard to efficacy, flexibility, and clinical applicability are discussed.