Protective CD8 T cell immunity triggered by CpG-protein conjugates competes with the efficacy of live vaccines
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
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