Antigen co-encapsulated with adjuvants efficiently drive protective T cell immunity.
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.
Heit
Antje
A
Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
Schmitz
Frank
F
Haas
Tobias
T
Busch
Dirk H
DH
Wagner
Hermann
H
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D019344:Lactic Acid / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008863:Microspheres; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D013601:T-Lymphocytes / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000941:Antigens; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D011108:Polymers; D051193:Toll-Like Receptors; D014614:Vaccines, Synthetic; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin