Antigen co-encapsulated with adjuvants efficiently drive protective T cell immunity

被引:105
作者
Heit, Antje
Schmitz, Frank
Haas, Tobias
Busch, Dirk H.
Wagner, Hermann
机构
[1] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany
[2] GSF Munich, Clin Res Grp Antigen Specif Immunotherapy, Munich, Germany
关键词
dendritic cells; T cells; vaccination;
D O I
10.1002/eji.200737169
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Compared to "live" vaccines, the immunogenicity of "subunit" vaccines based on recombinant antigen (Ag) is poor, presumably because exogenous Ag fails to effectively access the endosomal Ag-processing pathways of Ag-presenting cells (APC). To overcome this limitation, we exploited biodegradable poly(lactic-co-glycolic) microspheres (MP) co-entrapping Ag and Toll-like receptor (TLR) 9 or 7 ligands as an endosomal delivery device. In vitro, microspheres were rapidly phagocytosed by APC and translocated into phago-endosomal compartments, followed by degradation of the Ag and concurrent activation of endosomal TLR. As a consequence, full maturation of and cytokine secretion by APC as well as Ag-cross-presentation ensued. In vivo, "loaded" microspheres triggered clonal expansion of primary and secondary Ag-specific CD4 and CD8 T cells. The efficacy of CD8 T cell cross-priming was comparable to that of live vectors. The potency of T cell vaccination was demonstrated by protective and therapeutic interventions using infection- and tumor-model systems. These preclinical "subunit" vaccination data thus recommend MP as a generally applicable and powerful endosomal delivery device of exogenous Ag plus TLR-based adjuvants to vaccinate for protective and therapeutic CD4 and CD8 T cell immunity.
引用
收藏
页码:2063 / 2074
页数:12
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