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Protein subunit vaccines are an attractive mode of immunisation against infectious diseases but the approach is hampered by the lack of suitable adjuvants for human use. We investigated if antigen targeting to the endocytic cell receptor Dec-205 on dendritic cells (DCs) could induce a protective immune response to Mycobacterium tuberculosis (MTB) infection in the absence of conventional adjuvants...
Gram-negative bacterial outer membrane proteins (Omps) have an important role in pathogenesis and signal reception. We previously reported that Acinetobacter OmpA (AbOmpA) induced maturation of bone marrow-derived dendritic cells (BMDCs) and that AbOmpA-primed DCs produced IL-12 which generated Th1 CD4 + T-cells. We analyzed the effects of Salmonella typhimurium OmpA (OmpA-Sal) on dendritic...
CD4 + CD25 + regulatory T cells (Tregs) are known to inhibit immune responses to antigens. Since, the process of antigen uptake by dendritic cells (DC) is central to induction of immune responses, we analyzed the effect of Tregs on the expression of endocytic receptors on DC and its repercussion on antigen uptake. Our results demonstrate that Tregs down-regulate the expression and...
Recent evidence demonstrates that PEG10 plays an essential role in hepatocarcinogenesis and development, thus it could be regarded as a therapeutical target for hepatocellular carcinoma (HCC). In addition, transduction with recombinant, replication-defective adenoviral (Ad) vectors encoding tumor associated antigen into dendritic cells (DCs) is an efficient strategy to elicit antigen specific cytotoxic...
Virus-like particles (VLPs) are excellent tools for vaccines against pathogens and tumors. They can accommodate foreign polypeptides whose incorporation efficiency and immunogenicity however decrease strongly with the increase of their size. We recently described the CD8 + T cell immune response against a small foreign antigen (i.e., the 98 amino acid long human papilloma virus E7 protein)...
Peyer's patch have been extensively studied as a major inductive site for mucosal immunity within the small intestine. The intestinal mucosa contains numerous dendritic cells, which induce either protective immunity to infectious agents or tolerance to innocuous antigens, including food and commensal bacteria. Although during the past few years, several subsets of human mucosal dendritic cells have...
Main obstacles to cancer vaccine efficacy are pre-existing antigenic load and immunoescape mechanisms, including tolerance against self tumor-associated antigens. Here we explored the role of tolerance in an antimetastatic vaccine approach based on dendritic cell–tumor cell (DC–TC) hybrids, thanks to the comparison between BALB-neuT mice, transgenic for and tolerant to rat HER-2/neu, with their non-tolerant...
Potency testing is mandatory for vaccine registration and batch release. Due to various limitations to in vivo potency testing, there is need for relevant in vitro alternatives. These alternative tests should preferably comprise cells from the target (human) species. The whole suite of immune responses to vaccination that occur in vivo in humans cannot be tested in vitro using a single cell type....
We have reported that Surfacten ® (St), a bovine pulmonary surfactant free of antigenic c-type lectins, is a useful mucosal adjuvant for nasal vaccination. To prepare ample supplies a synthetic adjuvant that mimics St, we analyzed essential constituents of St for mucosal adjuvanticity. Intranasal inoculation of influenza virus hemagglutinin (HA) vaccine combined with St free of surfactant...
Vaccines that protect against intracellular infections such as malaria, Leishmania and Chlamydia require strong cellular responses based on CD4 + T cells and CD8 + T cells in addition to antibodies. Such cell-mediated responses can be potentiated with adjuvants. However, very few adjuvants have been licensed for use in humans; thus there is an urgent need for the discovery of new non-toxic...
Therapeutic immunization has been proposed as an approach that might help limit the need for lifelong combined antiretroviral therapy (cART). One approach for therapeutic vaccination which has been explored during the last few years is the administration of autologous monocyte-derived DCs (MD-DCs) loaded ex vivo with a variety of antigens. It has been shown in experimental murine models as well as...
Numerous evidence demonstrate Type 1 diabetes (T1D) is due to a loss of immune tolerance to islet antigens, and CD8 + T cells play an important role in the development of T1D in NOD mice. The novel coinhibitory receptor BTLA may have a regulatory role in maintaining peripheral tolerance, however, its role in autoimmune diabetes is unknown. To explore whether the generation of tolerance aiming...
Dendritic cells are the largest population of antigen presenting cells in the body. One of their main functions is to regulate the delicate balance between immunity and tolerance responsible for maintenance of immunological homeostasis. Disruption of this delicate balance often results in chronic inflammation responsible for initiation of organ specific autoimmune diseases such as rheumatoid arthritis,...
In this proof-of-concept study we report the use of <15nm, water soluble, inorganic nanoparticles as a vaccine delivery system for a blood stage malaria vaccine. The recombinant malarial antigen, Merozoite Surface Protein 1 (rMSP1) of Plasmodium falciparum served as the model vaccine. The rMSP1 was covalently conjugated to polymer-coated quantum dot CdSe/ZnS nanoparticles (QDs) via surface carboxyl...
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