Protective CD8 T cell immunity triggered by CpG-protein conjugates competes with the efficacy of live vaccines
- Author(s)
- Heit, A; Schmitz, F; O'Keeffe, M; Staib, C; Busch, DH; Wagner, H; Huster, KM;
- Details
- Publication Year 2005-04-01,Volume 174,Issue #7,Page 4373-4380
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- In contrast to infectious (live) vaccines are those based on subunit Ag that are notoriously poor in eliciting protective CD8 T cell responses, presumabily because subunit Ags become insufficiently cross-presented by dendritic cells (DCs) and because the latter need to be activated to acquire competence for cross-priming. In this study, we show that CpG-Ag complexes overcome these limitations. OVA covalently linked to CpG-DNA (CpG-OVA complex), once it is efficiently internalized by DCs via DNA receptor-mediated endocytosis, is translocated to lysosomal-associated membrane protein 1 (LAMP-1)-positive endosomal-lysosomal compartments recently shown to display competence for cross-presentation. In parallel, CpG-OVA complex loaded DCs become activated and acquire characteristics of professional APCs. In vivo, a single s.c. dose of CpG-OVA complex (10 mu g of protein) induces primary and secondary clonal expansion/contraction of Ag-specific CD8 T cells similar in kinetics to live vaccines; examples including Listeria monocytogenes genetically engineered to produce OVA (LM-OVA) and two viral vector-based OVA vaccines analyzed. Interestingly, CpG-OVA complex induced almost equal percentages of Ag-specific memory CD8 T cells as did infection with LM-OVA. A single dose vaccination with CpG-OVA complex protected mice against lethal doses of LM-OVA. These data underscore that the synergy imparted by CpG-OVA complex-mediated combined triggering of innate and specific immunity might be key to initiate CD8 T cell-based immunoprotection by synthetic vaccines based on subunit Ag.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- AIDED CROSS-PRESENTATION; HOST-RANGE SELECTION; TOLL-LIKE RECEPTORS; DENDRITIC CELLS; IMMUNOSTIMULATORY DNA; BACTERIAL-INFECTION; VIRUS ANKARA; ANTIGEN; EXPRESSION; TLR9
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Creation Date: 2005-04-01 12:00:00