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.
Heit
Antje
A
Institute for Medical Microbiology, Immunology and Hygiene, Trogerstrasse 30, D-81675 München, Germany.
Busch
Dirk H
DH
Wagner
Hermann
H
Schmitz
Frank
F
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D006801:Humans; D008863:Microspheres; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000941:Antigens; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D014612:Vaccines