We have worked to strengthen vaccine developments with an improved humanized mouse model. We focus on recombinant vaccines against HIV driven by a powerful poxvirus vaccine system termed MVA BN. To improve our understanding MVA BN has been analyzed thoroughly on the nucleotide level, safety in cell cultures, immune deficient mice as well as in healthy, HIV–infected and other immune deficient humans.

HLA-DP4/MAGE3 molecules have been prepared to stain ex vivo PBL from immunized melanoma patients for a study of anti-tumor responses in melanoma patients that were vaccinated with autologous DCs loaded with a combination of tumor Ag peptides.

Patients with resected HPV16-positive cervical cancer were vaccinated with an overlapping set of long peptides comprising the sequences of the HPV16 E6 and E7 oncoproteins emulsified in Montanide ISA-51.

Patients with resected HPV16-positive cervical cancer were vaccinated with an overlapping set of long peptides comprising the sequences of the HPV16 E6 and E7 oncoproteins emulsified in Montanide ISA-51.

HSV vector expressing full length tyrosinase, gp100 and MART-1optimised for antigen delivery to dendritic cells by the deletion of HSV genes which usually inhibit DC function. These deliver antigens to DC at very high efficiency and activate the transduced cells similarly to LPS. Biovex provides the possibility of using these vectors for a variety of pre-clinical, and ultimately clinical studies.

These dimers were injected into TCR transgenic mice which exhibited an increased frequency of LACK-specific T cells with the aim of producing a mAb reacting to the immunodominant LACK156-173 peptide of leishmania bound to I-Ad MHC class II molecules.

We have investigated the respective role of IL-10 and IDO, both required for Th1 suppression in this model. As IL-10 has been shown to indirectly dampen Th1 responses through the inhibition of IL-12 production by antigen-presenting-cells, we monitored mRNA expression specific for the inducible chain IL-12 p35 in lymph nodes draining the site of injection or in mesenteric lymph nodes of mice instilled intra-colonically with TNBS. Our results clearly show that IL-12 production early after the onset of the response was unaffected by anti-CTLA-4 treatment. By cont...

IFN alpha was used in a DC maturation process with the final aim to produce a DC vaccine.

We have investigated the respective role of IL-10 and IDO, both required for Th1 suppression in this model. As IL-10 has been shown to indirectly dampen Th1 responses through the inhibition of IL-12 production by antigen-presenting-cells, we monitored mRNA expression specific for the inducible chain IL-12 p35 in lymph nodes draining the site of injection or in mesenteric lymph nodes of mice instilled intra-colonically with TNBS. Our results clearly show that IL-12 production early after the onset of the response was unaffected by anti-CTLA-4 treatment. By cont...

It was shown that both IL-10 as well as IL-12 production is dependent on the signalling adaptor molecules either MyD88 or TRIF, respectively in response to CpG, LPS or PolyIC.

It was shown that both IL-10 as well as IL-12 production is dependent on the signalling adaptor molecules either MyD88 or TRIF, respectively in response to CpG, LPS or PolyIC.

Monocytes were transferred into culture bags by sterile welding and cultured for 5 days in serum free medium (CellGro, Cell Genix) in the presence of 100 ng/mL GM-CSF (Leukine, Berlex) and 20 ng/mL IL-4 (Cell Genix).

ImmunoVexHSV2 is a product for the prevention of infectious disease, it is a vaccine for genital herpes. In preclinical studies, ImmunoVex HSV2 completely prevents disease and invokes a powerful immune response.

We analysed the ability of invariant NKT (iNKT) cells to assist priming of antigen specific T and B cell responses. 1) We have demonstrated that activation of human DC by Toll like receptor ligands (TLR-L) modulates the lipid biosynthetic pathway, resulting in enhanced recognition of CD1d-associated lipids by iNKT cells. 2) We have clarified the mechanisms by which CD1d-restricted lymphocytes translate T cell receptor (TCR) recognition of lipids with similar group heads into distinct biological responses. Using a soluble iNKT TCR and a newly engineered anti...

Primed mice were treated with these antibodies. This treatment induced the development of regulatory T cells expressing high levels of ICOS and producing IL-10.

A long-standing collaboration with Centre for Ecology & Hydrology (CEH, UK) has led to the identification of an activity in salivary gland extracts of the tick Rhipicephalus appendiculatus that profoundly modulates the responses of human monocyte-DC towards extrinsic stimuli. The gene for this molecule, which we have termed Japanin, has been cloned and recombinant protein has been generated. This material inhibits the up-regulation of costimulatory molecules in response to certain TLR agonists, and some cytokines but not others, and modulates the function of...

2 mM L-glutamine (Sigma) was added to the monocyte cell culture.

Tetanus toxide epitope embedded into a L-SIGN/DC-SIGN-cross-reactive Ab was targeted to dendritic cells. We believe that the isolated Abs may be useful for selective delivery of Ags to DC-SIGN- or L-SIGN-bearing APCs for the modulation of immune responses and for blocking viral infections.

Laminarin (500 micrograms/ml) was added to DCs in order to block their beta-glucan receptors.

There are lentiviral vectors available in the lab.