Watch Now - VALIDATE Seminar: A Double Bill with Institut Pasteur de Tunis

About the Seminar: Two talks each followed by a Q&A

For our first VALIDATE Event of 2023, we have an exciting double bill: Two talks, covering two pathogens, from two VALIDATE members at the Institut Pasteur de Tunis, Tunisia. 

The two talks will be:

• Talk 1: Targeting FOXO3 transcription factor as a Host-Directed approach to enhance the efficacy of BCG against Mycobacterium tuberculosis with Prof Makram Essafi
  The failure of BCG to induce long-term protection has been endowed to its inability to escape the phagolysosome, leading to mild activation of CD8+ mediated T cell response. Induction of apoptosis in host cells plays an important role in potentiating dendritic cells-mediated priming of CD8+ T cells, a process defined as “cross-priming”. Moreover, IL-10 secretion by infected cells has been also reported to hamper BCG-induced immunity against Tuberculosis (TB). We previously reported that both, apoptosis of BCG-infected macrophages and inhibition of IL-10 secretion are FOXO3 dependent, a transcription factor negatively regulated by the pro-survival activated threonine kinase, Akt. We speculate that FOXO3 activation, during BCG vaccination, would enhance apoptosis and abrogate IL-10 secretion, leading to higher protection against Mtb. Here, we have assessed whether co-administration of a known anti-cancer Akt inhibitor (i.e, FOXO3 activator), MK-2206, enhances the protective efficacy of BCG in mice model of infection. We observed that in vitro MK-2206 treatment resulted in FOXO3 activation, enhanced BCG-induced apoptosis of macrophages and inhibition of IL-10 secretion. Co-administration of BCG along with MK-2206 also increased apoptosis of antigen-presenting cells in draining lymph nodes of immunized mice. Further, MK-2206 administration improved BCG-induced CD4+ and CD8+ effector T cells responses and its ability to induce both effector and central memory T cells. Finally, we show that co-administration of MK-2206 enhanced the protection imparted by BCG against Mtb in aerosol infected mice and guinea pigs. Taken together, we provide evidence that activation of FOXO3 potentiates BCG-induced immunity and imparts protection against Mtb through enhanced innate immune response.
• Talk2: Vaccine against Human Leishmaniasis: Institut Pasteur de Tunis Contribution with Prof Dhafer Laouini
  Leishmaniasis constitutes a heterogeneous group of diseases that affect millions of people and are caused by various Leishmania species. In terms of global disease burden, the leishmaniasis are one of the most important parasitic diseases The fact that the majority of individuals who have previously developed active leishmaniasis or asymptomatic infection are resistant to a subsequent clinical infection provides the rationale for vaccine development. Immunity against leishmaniasis depends on anti-parasite cellular immune responses involving CD4+ and CD8+ T cells conjointly with innate immunity. The proposed talk will describe the efforts made by Institute Pasteur de Tunis’ scientists towards the development of a broadly protective anti-Leishmania vaccine.

About the Speakers
 

Makram Essafi is a Professor in Immunology at Institut Pasteur de Tunis. Makram is leading a group working on the role of host innate response in the establishment of an efficient adaptive immune one against TB. The major aim is to uncover the host factors involved in such response to help generating tools to be used either as adjuncts for the standard treatment of TB or as adjuvants to enhance the efficacy of BCG. The data we generated led us to work on the development of better versions of BCG vaccine to prevent/treat Tuberculosis. 

 

 

Dhafer Laouini is a scientist at Institut Pasteur de Tunis. After obtaining his PhD in Immunology and Molecular Biology, he held several postdoctoral positions (Institute Pasteur, Paris, France and Harvard Medical School, Boston, USA), specializing in Immunology. He is currently heading the Group Immunobiology of Infections that focuses on the identification of correlates of protection in individuals at risk, the use of omics approaches to investigate host-pathogen interactions and the study of innate and adaptive immune responses induced by vector components. He is also working on the development of non-invasive, safe and patient-friendly tools for on-site rapid diagnosis of cutaneous leishmaniasis. 

 

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