Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants.

International audienceVaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the development of new safe adjuvants and vaccine platforms. Of particular interest, the utilization of plant virus-like nanoparticles and recombinant plant viruses has gained increasing significance as an effective tool in the development of novel vaccines against infectious diseases and cancer. The present review summarizes recent advances in the use of plant viruses as nanoparticle-based vaccines and adjuvants and their mechanism of action. Harnessing plant-virus immunogenic properties will enable the design of novel, safe, and efficacious prophylactic and therapeutic vaccines against disease

The papaya mosaic virus (PapMV) nanoparticles; a promising tool in vaccine development.

There is a major need for the development of new technologies that will facilitate the speed of development of vaccine and show a very high safety profile. In the last 10 years, we have developed a new toll like receptor agonist (TLR) that can trigger innate immunity follow by a strong adaptive immune response. This new agonist targets specifically the TLR7/8 in the endosome of the immune cells. It is made of the coat protein (CP) of a plant virus self-assembled around an RNA that forms flexuous rod-shape nanoparticles of 15x100nm. The highly repetitive and crystalline nature of the nanoparticles are attractive to immune cells leading to its internalization into the endosome where the nanoparticles is broken down by the harsh conditions of this compartment which liberate the RNA that trigger TLR7/8 to induce innate immunity. Therefore, we can use those nanoparticles as an adjuvant and improve the immune response to an antigen or as an immune modulator through the trigger of innate immunity that can induce protection to viral infection or improve the immune response to tumour. Finally, we have showed that we can engineered the nanoparticles into a vaccine platform through fusion of B or T cell epitope at its surface and elicits an efficient and protective immune response to the fused epitope. We will discuss the advantage of using this platform in vaccine development or cancer immunotherapy and show several examples where it has been shoed to be efficient and promising

Expression of Viral Antigen by the Liver Leads to Chronic Infection Through the Generation of Regulatory T Cells

Referred to by David E. Kaplan " Does Massive Antigen Burden Allow Hepatic Viruses to Induce Regulatory T Cells and Their Tolerance and Persistence?" CMGH Cellular and Molecular Gastroenterology and Hepatology, Volume 1, Issue 3, May 2015, Pages 259-261International audienceThe constant exposure of the liver to food and bacterial antigens through the mesenteric circulation requires it to maintain tolerance while preserving the ability to mount an effective immune response against pathogens. We investigated the contribution of the liver's tolerogenic nature on the establishment of chronic viral infections. Methods: TTR-NP mice, which express the nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) specifically in hepatocytes under control of a modified transthyretin (TTR) promoter, were infected with the Armstrong (Arm) or WE acute strains of LCMV. Results: The infection persisted for at least 147 days in TTR-NP mice. Expression of NP by the liver induced a strong peripheral tolerance against NP that was mediated by interleukin-10-secreting CD4+ regulatory T cells, leading to high PD-1 (programmed death-1) expression and reduced effector function of virus-specific T cells. Despite an active immune response against LCMV, peripheral tolerance against a single viral protein was sufficient to induce T-cell exhaustion and chronic LCMV Armstrong (Arm) or WE infection by limiting the antiviral T-cell response in an otherwise immunocompetent host. Regulatory T-cell depletion of chronically infected TTR-NP mice led to functional restoration of LCMV-specific CD4+ and CD8+ Tcell responses and viral clearance. Conclusions: Expression of a viral antigen by hepatocytes can induce a state of peripheral tolerance mediated by regulatory Tcells that can lead to the establishment of a chronic viral infection. Strategies targeting regulatory T cells in patients chronically infected with hepatotropic viruses could represent a promising approach to restore functional antiviral immunity and clear infection

Histoire des bibliothécaires

Le Centre de recherche en histoire du livre a souhaité redynamiser le domaine scientifique de l\u27histoire des bibliothèques. Avec ce colloque consacré à l\u27histoire des bibliothécaires, il aborde l\u27une des composantes essentielles d\u27une histoire des bibliothèques qui, paradoxalement, n\u27avait jamais retenu l\u27attention des historiens, tant en France qu\u27à l\u27étranger. Le colloque couvre la période du Moyen Âge à aujourd\u27hui, et est construit dans une perspective directe d\u27histoire comparée. Il se compose de trois parties : 1. Bibliothèque religieuse, bibliothèque savante, bibliothèque nationale 2. Bibliothécaires des Lumières 3. Figures de la modernit

Cyclophilin D Regulates Antiviral CD8+ T Cell Survival in a Cell-Extrinsic Manner

CD8+ T cell–mediated immunity is critical for host defense against viruses and requires mitochondria-mediated type I IFN (IFN-I) signaling for optimal protection. Cyclophilin D (CypD) is a mitochondrial matrix protein that modulates the mitochondrial permeability transition pore, but its role in IFN-I signaling and CD8+ T cell responses to viral infection has not been previously explored. In this study, we demonstrate that CypD plays a critical extrinsic role in the survival of Ag-specific CD8+ T cell following acute viral infection with lymphocytic choriomeningitis virus in mice. CypD deficiency resulted in reduced IFN-I and increased CD8+ T cell death, resulting in a reduced antiviral CD8+ T cell response. In addition, CypD deficiency was associated with an increase in pathogen burden at an early time-point following infection. Furthermore, our data demonstrate that transfer of wild-type macrophages (expressing CypD) to CypD-deficient mice can partially restore CD8+ T cell responses. These results establish that CypD plays an extrinsic role in regulating optimal effector CD8+ T cell responses to viral infection. Furthermore, this suggests that, under certain circumstances, inhibition of CypD function may have a detrimental impact on the host’s ability to respond to viral infection

Regulation of activation-induced deaminase stability and antibody gene diversification by Hsp90

Hsp90 stabilizes and prevents degradation of cytoplasmic activation-induced deaminase