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

Eur J Immunol. 2007 Aug;37(8):2063-74. doi: 10.1002/eji.200737169.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic* / chemical synthesis
  • Animals
  • Antigen Presentation / immunology
  • Antigens / immunology
  • Dendritic Cells / immunology
  • Endosomes / immunology
  • Endosomes / metabolism
  • Lactic Acid / immunology
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Microspheres*
  • Oligodeoxyribonucleotides / immunology
  • Ovalbumin / immunology
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers
  • T-Lymphocytes / immunology*
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism
  • Vaccines, Synthetic / immunology*


  • Adjuvants, Immunologic
  • Antigens
  • CPG-oligonucleotide
  • Oligodeoxyribonucleotides
  • Polymers
  • Toll-Like Receptors
  • Vaccines, Synthetic
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Ovalbumin