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Bacterial DNA differs from vertebrate DNA in having a much higher content of unmethylated CpG dinucleotides, in particular, base contexts that are termed ‘CpG motifs’. The vertebrate immune system appears to have evolved pattern recognition molecules that recognize ‘CpG motifs’ as foreign, and trigger protective immune responses which are strongly Th1-biased. These responses can be mimicked using...
Recently, a dual receptor agonist for human Flt3 and G-CSF receptors, progenipoietin-4 (ProGP-4), was shown to be highly effective in expanding DC in vivo. In this study, we examined the immunological activity of ProGP-4-generated dendritic cell (DC) in an HLA-A2.1 transgenic mouse system. ProGP-4 DC were found to be approximately equivalent in presenting a cytotoxic T lymphocyte (CTL) peptide to...
Human papilloma virus (HPV) found in 99.7% of cervical cancers represents an attractive immunotherapeutic target for novel adjuvant dendritic cell (DC) immunotherapy. DC primed with HPV antigens have been shown to be capable of inducing CTL responses powerful enough to eradicate established murine tumours expressing HPV16 antigen. The use of tumour lysate has been found to be an effective means of...
We have studied the effects of adjuvant formulations on the activation and antigen-presenting functions of bone marrow-derived dendritic cells (DCs). While LPS could induce high-level expression of MHC Class II and co-stimulator molecules on DCs, it did not enhance antigen presentation to co-stimulation independent DO11.GFP T hybridoma cells. In contrast, alum, NISV and PLGA formulations failed to...
For the rational design of vaccines capable of inducing CD8 + T cell responses knowledge of the identity of the antigen-presenting cell (APC) and the mechanism of antigen presentation is very important. Here, we address these issues for alphavirus-based immunization, in particular immunization with recombinant Semliki Forest virus (rSFV). Studies with dendritic cells (DCs) from various origins...
Dendritic cells (DC) become fully functional upon maturation by various stimuli. We tested whether an immunostimulatory effect of clinically used immunomodulators (Luivac ( R), Biostim ( R), Ribomunyl ( R), Imudon ( R), Bronchovaxom ( R)) is caused by direct DC activation. We found that Luivac ( R), Biostim ( R) and Ribomunyl ( R) have...
The only available vaccine against tuberculosis (TB) is Bacillus Calmette-Guérin (BCG) whose efficacy in preventing pulmonary tuberculosis is however controversial. Here, we show that BCG infection of monocytes causes their differentiation into mature dendritic cells (DCs) lacking CD1 molecules expression, coupled with suboptimal up-regulation of HLA class II, CD80 and CD40 molecules and a marked...
The intestinal immune system discriminates between invasive pathogens and antigens that are harmless, such as food proteins and commensal bacteria. The latter groups of antigens normally induce tolerance and the nature of the intestinal immune response depends on how antigen is presented to CD4 + T cells by dendritic cells (DC). Expanding the numbers of DC in vivo using the cytokine flt3 ligand...
A population of cells exhibiting bona fide dendritic cell (DC) morphological and functional characteristics was obtained by treating Aotus spp. monocytes with human IL-4 and GM-CSF. Although the purity of mature DCs was relatively low IL-4/GM-CSF-treated monocytes (hereafter called Aotus spp. DCs) down-regulated CD14 and up-regulated discrete levels of CD80, MHC-Class II and CD1b molecules in response...
In order to improve the efficacy of current vaccine candidates against HIV/AIDS, we sought to strengthen the induction of immune responses via simultaneous in vivo mobilization of dendritic cells using a chimeric Flt-3 and G-CSF receptor agonists (ProGP). We investigated ProGP treatment in combination with two DNA immunizations encoding HIV-Env89.6, SIV-Gag proteins to increase the priming of immune...
The aim of this experiment was to develop a cytotoxic cancer vaccine (EC109-DC) prepared by fusions of esophageal carcinoma cells with dendritic cells derived from cord blood and to study the biological characteristics and resultant induction of antitumor immunity. CD34 + hematopoietic stem cells were isolated from cord blood using a CD34 + Progenitor Cell Isolation Kit by magnetic...
Recombinant adenoviruses (rAds) represent a promising system for vaccine delivery but transduce dendritic cells (DC) relatively poorly. To address this concern, we used a biotin–avidin linkage to conjugate rAd vectors to ligands which bind with high affinity to selected receptors on DC (ChemR23, α v β 3 integrin, and DC-SIGN). The targeted vectors had an enhanced ability to transduce...
Immunogenic peptide-based vaccines can raise significant cellular immune responses. Although cytotoxic T lymphocytes (CTL) peptide epitopes are generally poor immunogens, heat shock protein 70 from Mycobacterium tuberculosis (TBhsp70) can overcome this problem since it is a potent adjuvant that links innate and adaptive immune responses. Our goal is to use TBhsp70 as an adjuvant for development of...
To better understand immune modulation by endotoxin and facilitate the development of novel vaccine adjuvants, the structural requirements of Neisseria meningitidis lipopoly(oligo)saccharide (LOS) for activation of human monocyte derived dendritic cell (MDDC) was determined. Highly purified LOS from wild type and genetically-defined mutants of N. meningitidis serogroup B were used. Unglycosylated...
Fusing dendritic cells (DCs) with tumor cells is a powerful vaccine to increase tumor immunogenicity. To develop more effective and safer therapeutic vaccine, we fused rat bone marrow-derived DCs with ovarian tumor cell line NuTu-19 modified by suicide gene (HSV 1 -TK gene) to obtain live vaccine against ovarian cancer. Our data showed that immunization of rats with such live vaccine solicited...
DNA vaccination is an attractive approach with various advantages over conventional vaccination. The present study was undertaken to examine whether polyplex-based DNA vaccination could be used to modulate immune responses by plasmid DNA (pDNA). Methylated bovine serum albumin (mBSA) was used as a model of a cationic macromolecular carrier of pDNA encoding obalbumin (OVA) and the effects of polyplex...
Previous studies demonstrated that allergen gene vaccination induced TH1-skewed responses and inhibited IgE production. This study evaluated and characterized the immune responses induced by three DNA constructs encoding different forms of Der p 2 for safe and efficacious vaccination against mite allergy.Mice were immunized intramuscularly with DNA constructs encoding a major mite allergen, Der p...
To determine the dynamics of dendritic cell (DCs) migration and their role in recurrent infections by nontypeable Haemophilus influenzae (NTHi), the migration of mature DC into pulmonary lymph nodes (LN) and the development of a P6-specific immune response and bacterial clearance in the lung were examined after repeated airway challenges with outer membrane protein (OMP) at 1-week intervals in mice...
The poxviruses including canarypox (ALVAC) and vaccinia viruses are promising vaccine vectors in humans, but little is known about their biology in human cells. Using recombinant enhanced green fluorescence protein (EGFP)-expressing ALVAC and vaccinia viruses, we have focused here on a side-by-side comparison of ALVAC and vaccinia virus tropism for cells from human peripheral blood and bone marrow...
We investigated the mechanism by which ALVAC activates innate immunity. Combining ALVAC with protein antigens significantly augmented antigen-specific IgG2a responses; this was dependent on the presence of bioactive interferon (IFN)-γ. Immuno-depletion of NK cells prior to ALVAC immunisation abrogated IFN-γ production indicating that they are the main cellular source of early IFN-γ in vivo. Murine...
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