Bacterium-like particles as multi-epitope delivery platform for Plasmodium berghei circumsporozoite protein induce complete protection against malaria in mice

Contains fulltext : 110364.pdf (publisher's version ) (Open Access)BACKGROUND: Virus-like particles have been regularly used as an antigen delivery system for a number of Plasmodium peptides or proteins. The present study reports the immunogenicity and protective efficacy of bacterium-like particles (BLPs) generated from Lactococcus lactis and loaded with Plasmodium berghei circumsporozoite protein (PbCSP) peptides. METHODS: A panel of BLP-PbCSP formulations differing in composition and quantity of B-cell, CD4+ and CD8+ T-cell epitopes of PbCSP were tested in BALB/c mice. RESULTS: BLP-PbCSP1 induced specific humoral responses but no IFN-gamma ELISPOT response, protecting 30-40% of the immunized mice. BLP-PbCSP2, with reduced length of the non-immunogenic part of the T-cell-epitopes construct, increased induction of IFN-gamma responses as well as protection up to 60-70%. Compared to controls, lower parasitaemia was observed in unprotected mice immunized with BLP-PbCSP1 or 2, suggestive for partial immunity. Finally, further increase of the number of B-cell epitopes and codon optimization (BLP-PbCSP4) induced the highest anti-CSP antibody levels and number of IFN-gamma spots, resulting in sterile immunity in 100% of the immunized mice. CONCLUSION: Presentation of Plasmodium-derived antigens using BLPs as a delivery system induced complete protection in a murine malaria model. Eventually, BLPs have the potential to be used as a novel versatile delivery platform in malaria vaccine development

Cationic liposomes as DNA delivery system. Characterization of SAINT-mediated gene transfer

The work presented in this thesis was aimed at characterizing cationic liposome-mediated transfection and, more specifically, investigated the properties of the synthetic cationic lipid SAINT-2. In this final chapter, the data obtained with SAINT-2 containing liposomes will be summarized and discussed. Some perspective concerning the future application of cationic liposomes in different gene therapy approaches will also be presented. Zie: Summary.

Development of a dried influenza whole inactivated virus vaccine for pulmonary immunization

Stabilization and ease of administration are two ways to substantially improve the use of current vaccines. In the present study an influenza whole inactivated virus (WIV) vaccine was freeze-dried or spray-freeze dried in the presence of inulin as a cryoprotectant. Only spray-freeze drying rendered powders compatible with administration to the lungs by insufflation. Pulmonary administration of the powder vaccine obtained by this method to BALB/c mice led to a transient influx of neutrophils and a concomitant decrease in the number of macrophages as did administration of liquid vaccine. Inflammatory reactions to both vaccines were mild and short-lived. Immunization studies showed that the immunogenic properties of WIV vaccine were not affected by drying. Pulmonary administration of the powder WIV vaccine induced a systemic immune response of the same magnitude as liquid vaccine while mucosal IgA responses were higher for powder WIV. In a challenge study where immunized mice were exposed to a lethal dose of live virus, two pulmonary doses of either liquid or powder WIV vaccine were equally effective as a single intramuscular injection of subunit vaccine in terms of reduction of the viral load in the lungs. To conclude, in the models employed for these studies the use of a dry powder WIV vaccine for pulmonary immunization was shown to be safe and efficient. (C) 2011 Elsevier Ltd. All rights reserved

Cationic Amphiphiles as Delivery System for Genes into Eukaryotic Cells

Cationic liposomes, consisting of synthetic amphiphiles and a socalled helper lipid, rapidly form complexes with DNA, known as lipoplexes. When incubated with cells in culture, the DNA can be delivered into the cell and becomes expressed. Because of these properties, lipoplexes are considered a useful alternative for viral vectors for in vivo genetherapy. Yet, many hurdles have still to be taken. These are illustrated in the present overview, which briefly describes the critical steps involved in overall gene delivery in vitro, ranging from lipoplex formation to nuclear penetration and delivery of the desired gene.

Quels liens entre relation au lieu et concernement ? Une exploration interdisciplinaire vis-à- vis des risques fluviaux et côtiers en France métropolitaine

International audienceWhat are the links between the ”sense of place” of individuals and their “concern” about phenomena described as "risk" on French coasts? A state of the art specifies the concept of ”sense of place” and its different dimensions (identity, emotional, symbolic, functional) as well as the notion of “concern” and its modalities (passive or active). Based on these precisions, as wells as on data from different surveys conducted on French coastal and estuarine areas, we empirically characterize the dimensions of sense of place and their links with the modalities of environmental concern. The results show negative links between the symbolic and emotional dimensions of relation to place and a concern qualified as passive, as well as positive links between the symbolic dimension of relation to place and a so-called active concern. We discuss these relationships as well as their consequences for costal and territorial risks governance.Quels sont les liens entre la relation au lieu que développent des individus et leur « concernement » à propos de phénomènes qualifiés de « risques » sur ce même lieu ? Afin de répondre à cette question, un état de l’art précise tout d’abord le concept de « concernement » en qualifiant différentes modalités (notamment « passif » ou « actif ») ainsi que le concept de « relation au lieu » et ses différentes dimensions (identitaire, émotionnelle, symbolique, fonctionnelle) . Sur la base de ces précisions, et à partir des données issues de différentes enquêtes menées sur les littoraux français, une analyse est ensuite menée pour explorer empiriquement les liens entre différentes dimensions de la relation au lieu et les modalités de concernement vis-à-vis des risques fluviaux et côtiers. Les résultats montrent des liens négatifs entre les dimensions symboliques et émotionnelles de la relation au lieu et un concernement qualifié de passif, ainsi que des liens positifs entre la relation symbolique au lieu et un concernement dit actif. Ces relations sont enfin discutées par rapport aux implications de ce type de résultats dans des processus de gouvernance.Abstrac