Research Guido Vanham

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Pannus Pieter

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The general aim of this project is the design of an improved mRNA platform in order to enhance both the strength and the breadth of HIV-1 Gag-specific T cells. To this end, we will develop strategies that act to increase antigen translation and Tcell co-stimulation on the one hand, and on the other hand to improve antigenic coverage. Taken together, these approaches will result in a superior mRNA vaccine that could ultimately develop into a universal immunotherapy against HIV-1.

Researcher(s)

• Promoter: Vanham Guido

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

A recent study of our group indicated that it is safe to immunize HIV-1 infected patients with dendritic cells (DC) loaded with mRNA encoding subtype B consensus Gag or chimeric Tat-Rev-Nef. An increase in the antiviral cellular immune responses was observed. The aim of this project is to further optimize the DC vaccination strategy. This will be done using: - A more stable mRNA, - An antigen or combination of antigens to induce immune responses directed at different variants worldwide - Co-stimulatory signals to improve the DC immunogenicity.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Bracke Lotte

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: De Haes Winni

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

A recent study of our group indicated that it is safe to immunize HIV-1 infected patients with dendritic cells (DC) loaded with mRNA encoding subtype B consensus Gag or chimeric Tat-Rev-Nef. An increase in the antiviral cellular immune responses was observed. The aim of this project is to further optimize the DC vaccination strategy. This will be done using: - A more stable mRNA, - An antigen or combination of antigens to induce immune responses directed at different variants worldwide - Co-stimulatory signals to improve the DC immunogenicity.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Bracke Lotte

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

As the number of HIV-1 infections worldwide is still rising, there is an urgent need for microbicides which are vaginal formulations used by women to prevent heterosexual HIV transmission. Within this project, inhibitors of HIV-1 reverse transcription, integration and entry are evaluated as potential microbicides in vitro.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Selhorst Philippe

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

We aim to increase the immunogenicity of the HIV envelope by generating CD4-independent viruses and by inducing resistance to entry and fusion inhibitors. The working hypothesis is that in this way we force the virus to adopt a more open conformation, resulting in the exposure of more conserved regions of Env, which should facilitate the induction of broad cross-neutralizing antibodies.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Grupping Katrijn

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Vanham Guido
• Fellow: De Haes Winni

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The search for a HIV vaccine, able to induce broad cross-neutralizing antibodies (BCNA) remains a top priority. BCNA can be found in a minority of chronically HIV-infected subjects. Based on their plasma, we will select the responsible epitopes, based o, a "peptide phage display" method. On the other hand, we have at our disposal several "antibody phage libraries", based on the bone marrow of patients with BCNA. Therefore, it will be possible to isolate new BCNA via the previously selected peptides. Possible applications include the development of a multi-component vaccine and therapeutic antibodies

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Dieltjens Tessa

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The aim is to better understand the mechanisms of HIV transmission in the female genital tract by the development of an "in vitro dual chamber model". In the apical chamber, various epithelial cell lines, representative of the different compartments of the female genital tract, are grown to confluence on a semi-permeable membrane. In the basal chamber primary target cells, including macrophages, dendritic cells and T cells, are present. In this system, we can check which are the determinants of transmission of both cell-free and cell-associated HIV and we can also investigate how to block transmission of course. The latter is important in the development of new preventive stategies.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Gali Youssef

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The proposed PhD projects fits into the development of immunotherapy with dendritic cells in HIV-infected subjects under highly active anti-retroviral therapy (HAART). The specific aims are the following: 1)Define the correlates of protective T cell immunity in "secondary controllers", subjects who suppress HIV after stopping HAART. 2)In vitro induction of protective responses, based on co-cultures of T cells and dendritic cells (DC), transfected with mRNA encoding autologous HIV proteins 3)In vivo evaluation of safety and immunogenicity of DC in a SIV macaques model and in a phase 1 study of patients under HAART

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Selhorst Philippe

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The aim is to contribute to the development of anti-HIV drugs that could be used preventively in a vaginal application by women. A number of candidate-microbicides has been proposed in a European program, which also provides a PhD scholarship to Katty Terrazas. It is our task to test the candidates in an in vitro model, using primary dendritic cells and T cells. Products with a favorable therapeutic index will be tested for synergism. In addition we want to avoid cross-resistance with therapeutic drugs.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Terrazas Aranda Katty

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Developing new therapeutic strategies against HIV is a high priority: 80% of patients have developed resistance to some of the current drugs and transmission of drug-resistant virus is becoming a threat. While not aiming to evaluate new therapies in the clinic, this project will provide the basic research needed for the development of the following new treatment strategies.

Researcher(s)

• Promoter: Berneman Zwi
• Co-promoter: Vanham Guido
• Co-promoter: Van Tendeloo Vigor

Research team(s)

Project type(s)

• Research Project

Abstract

The search for a HIV vaccine, able to induce broad cross-neutralizing antibodies (BCNA) remains a top priority. BCNA can be found in a minority of chronically HIV-infected subjects. Based on their plasma, we will select the responsible epitopes, based o, a "peptide phage display" method. On the other hand, we have at our disposal several "antibody phage libraries", based on the bone marrow of patients with BCNA. Therefore, it will be possible to isolate new BCNA via the previously selected peptides. Possible applications include the development of a multi-component vaccine and therapeutic antibodies.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Dieltjens Tessa

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The aim is to better understand the mechanisms of HIV transmission in the female genital tract by the development of an "in vitro dual chamber model". In the apical chamber, various epithelial cell lines, representative of the different compartments of the female genital tract, are grown to confluence on a semi-permeable membrane. In the basal chamber primary target cells, including macrophages, dendritic cells and T cells, are present. In this system, we can check which are the determinants of transmission of both cell-free and cell-associated HIV and we can also investigate how to block transmission of course. The latter is important in the development of new preventive stategies.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Gali Youssef

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Following primary infection a vigorous HIV-specific CD8+ T-cell immune response is initiated. Nevertheless HIV can escape an efficient immune response resulting in the development of a chronic disease, which causes depletion of CD4+ and CD8+ T-cells. The recent highly active anti-retroviral therapy (HAART) is unable to eliminate the virus. Therefore, it is important to develop novel therapies, which are based on the induction of an effective immune response that is able to eliminate infected cells or control the virus lifelong. In this project we want to develop this strategy in vitro. The two crucial elements are: - Using a broad range of possible virus sequences of the latent reservoir as antigen, to protect again virus escape. To express the whole latent reservoir, a PCR based technology will be developed to amplify provirus Gag DNA from infected autologous T-cells. - An optimalisation of the antigen presentation by dendritic cells, by modifying the dendritic cells with costimulatory molecules, to improve the CD4 and CD8 T-cell dysfunction.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Van Gulck Ellen

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

This project has two equivalent main objectives: (1) To investigate the pathogenesis of clinical complications of Human T Lymphotropic Virus-l (HTL V-I ) in Peru. (2) To strengthen the academic capacity of the Institute of Tropical Medicine Alexander Von Humboldt in Lima. The strength of the research part relies on two elements: (a) the accessibility of a large patient cohort in Lima, with three types of complications (inflammatory, neoplastic and opportunistic infections) and the availability of asymptomatic HTLV-l-infected as well as -uninfected family members; (b) the integrated multidisciplinary approach to clinical, virological, immunological and genetic research questions. Using this research project as a "leverage", the diagnostic and clinical capacities of ITMA vH will grow and several young Peruvian technicians, clinicians, PhD students and one postdoc will be trained with the ultimate goal to constitute an intermediary academic staff who will be able to conceive and execute basic and clinical research in endemic infectious diseases. Basic knowledge on HTLY-l, as well as the guidelines resulting from this project will be extended to the Peruvian medical community and the health authorities.

Researcher(s)

• Promoter: Vanham Guido

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The present PhD projects fits into the EMPRO project, which aims to develop new candidate microbicides (preventive anti-HIV drugs). The specific EMPRO objectives are (1) To design new compounds that target several steps in the viral cycle before integration; (2) To compare their activity and toxicity in a number of in vitro and in vivo models; (3) To test a few selected compounds in human phase I trials. Our task in this project is to test products in a model system that mimics the most important target cells during sexual transmission: dendritic cells and autologous CD4 T cells. We already identified some active and non-toxic compounds in the various classes. The first scientific question for this PhD project is whether combinations of good compounds from different classes show synergistic action in our model system, without inducing excess toxicity. The ultimate purpose is that microbicides will be very widely available. One unwanted consequence could be the transmission of resistant viruses, since seropositive women, not aware of their status, might also use the products. Therefore, a second focus of our project will be to compare the candidate microbicide in our in vitro model for their potency in HIV resistance induction. Clearly, amongst equally active and non-toxic candidates, we will select those that do not easily induce resistance.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Terrazas Aranda Katty

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The power of the human immune system can be applied for the development of more specific immunotherapy for cancer and HIV infection. We will investigate the immunostimulatory potential of human dendritic cells (DC) loaded with tumor or HIV antigens in vitro. Knowledge regarding the DC-induced immune response can be used for the development of more effective therapeutic vaccines for cancer and HIV.

Researcher(s)

• Promoter: Berneman Zwi
• Co-promoter: Vanham Guido
• Co-promoter: Van Tendeloo Vigor

Research team(s)

Project type(s)

• Research Project

Abstract

Following primary infection a vigorous HIV-specific CD8+ T-cell immune response is initiated. Nevertheless HIV can escape an efficient immune response resulting in the development of a chronic disease, which causes depletion of CD4+ and CD8+ T-cells. The recent highly active anti-retroviral therapy (HAART) is unable to eliminate the virus. Therefore, it is important to develop novel therapies, which are based on the induction of an effective immune response that is able to eliminate infected cells or control the virus lifelong. In this project we want to develop this strategy in vitro. The two crucial elements are: - Using a broad range of possible virus sequences of the latent reservoir as antigen, to protect again virus escape. To express the whole latent reservoir, a PCR based technology will be developed to amplify provirus Gag DNA from infected autologous T-cells. - An optimalisation of the antigen presentation by dendritic cells, by modifying the dendritic cells with costimulatory molecules, to improve the CD4 and CD8 T-cell dysfunction.

Researcher(s)

• Promoter: Vanham Guido
• Fellow: Van Gulck Ellen

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project