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The secreted malarial protein, Cell-Traversal protein for Ookinetes and Sporozoites (CelTOS), is highly conserved among Plasmodium species, and plays a role in the invasion of mosquito midgut cells and hepatocytes in the vertebrate host. CelTOS was identified as a potential protective antigen based on a proteomic analysis, which showed that CelTOS stimulated significant effector T cells producing IFN-γ in peripheral blood mononuclear cells (PBMCs) from radiation attenuated sporozoite-immunized, malaria-naïve human subjects. In a rodent malaria model, recombinant full-length CelTOS protein/adjuvant combinations induced sterile protection, and in several studies, functional antibodies were produced that had hepatocyte invasion inhibition and transmission-blocking activities. Despite some encouraging results, vaccine approaches using CelTOS will require improvement before it can be considered as an effective vaccine candidate. Here, we report on the use of mRNA vaccine technology to induce humoral and cell-mediated immune responses using this antigen. Several pfceltos encoding mRNA transcripts were assessed for the impact on protein translation levels in vitro. Protein coding sequences included those to evaluate the effects of signal sequence, N-glycosylation on translation, and of nucleoside substitutions. Using in vitro transfection experiments as a pre-screen, we assessed the quality of the expressed CelTOS target relative to the homogeneity, cellular localization, and durability of expression levels. Optimized mRNA transcripts, which demonstrated highest protein expression levels in vitro were selected for encapsulation in lipid nanoparticles (LNP) and used to immunize mice to assess for both humoral and cellular cytokine responses. Our findings indicate that mRNA transcripts encoding pfceltos while potent for inducing antigen-specific cellular cytokine responses in mice, were less able to mount PfCelTOS-specific antibody responses using a two-dose regimen. An additional booster dose was needed to overcome low seroconversion rates in mice. With respect to antibody fine specificities, N-glycosylation site mutated immunogens yielded lower immune responses, particularly to the N-terminus of the molecule. While it remains unclear the impact on CelTOS antigen as immunogen, this study highlights the need to optimize antigen design for vaccine development.

A number of preclinical and clinical studies have demonstrated the efficiency of mesenchymal stromal cells to serve as an excellent base for a cell-mediated drug delivery system. Cell-based targeted drug delivery has received much attention as a system to facilitate the uptake a nd transfer of active substances to specific organs and tissues with high efficiency. Human mesenchymal stem cells (MSCs) are attracting increased interest as a promising tool for cell-based therapy due to their high proliferative capacity, multi-potency, and anti-inflammatory and immunomodulatory properties. In particular, these cells are potentially suitable for use as encapsulated drug transporters to sites of inflammation. Here, we studied the in vitro effects of incorporating synthetic polymer microcapsules at various microcapsule-to-cell ratios on the morphology, ultrastructure, cytokine profile, and migration ability of human adipose-derived MSCs at various time points post-phagocytosis. The data show that under appropriate conditions, human MSCs can be efficiently loaded with synthesized microcapsules without damaging the cell’s structural integrity with unexpressed cytokine secretion, retained motility, and ability to migrate through 8 μm pores. Thus, the strategy of using human MSCs as a delivery vehicle for transferring microcapsules, containing bioactive material, across the tissue–blood or tumor–blood barriers to facilitate the treatment of stroke, cancer, or inflammatory diseases may open a new therapeutic perspective.

Using the BRST approach to higher spin field theories we develop a generic technique for constructing the cubic interaction vertices for N=1 supersymmetric massless higher spin fields on four, six and ten dimensional flat backgrounds. Such an approach allows formulation of the equations for cubic vertices including bosonic and fermionic higher spin fields, and the problem of finding the vertices is reduced to finding the consistent solutions to these equations. As a realization of this procedure, we present the particular solutions for the vertices where the fields obey some off-shell constraints. It is shown that the supersymmetry imposes additional constraints on the vertices and singles out a particular subclass of the solutions. As a concrete application of the generic scheme, we consider supersymmetric Yang-Mills-like systems in four, six and ten dimensions where the higher spin fields transform under some internal symmetry group, as well as supergravity-like systems in the same dimensions.

Postweaning short-term restriction strategies are commonly used in rabbit breeding to reduce mortality and morbidity. However, little is known about the implications of the immune system in that reduction. This work studied the consequences of feed restriction and dietary digestible energy (DE) concentration on the local immune response, according to a 2x2 factorial design: 320 animals were alloted at weaning (35 days of age) in four groups, with two diets differing in DE (10.13 vs 9.08 MJ DE/kg) and two intake level (ad libitum "AL" or restricted at 75% of AL). Ten animals per group and per age were sacrificed at 50 and 63 days of age. Feces, blood and ileum were collected. Fecal and plasmatic IgA levels were determined by ELISA and ileal cytokine expressions were measured by RT-qPCR. Fecal IgA levels were reduced by 58% with feed restriction (P

National audience

Restricted feeding is commonly used in rabbit breeding to reduce mortality and morbidity but results in decreased growth and lower slaughter yield. A high energy diet offered at 75% of the ad libitum (AL) intake could prevent these detrimental effects. The aim of this work was to study the consequences of such a feeding strategy on the digestive efficiency of growing rabbits. 48 animals were divided into four groups differing in dietary energy content (2417 (HE) vs 2168 kcal DE/kg GM) and feeding level (AL or restricted at 75% (R)) according to a 2x2 experimental design. Animals were fed the experimental diets from weaning (35 d of age) to 74 d of age, and feed restriction was applied from 35 to 63 d. Digestive efficiency was assessed during feed restriction (42 to 46 d) and after one week of AL feeding (70 to 74 d). Feed restriction improved fecal digestibility of organic matter (OM, +3.8pts), protein (+5.4pts) and fiber (NDF +5.5pts, ADF +5.9pts; p

International audience

Cells of the dendritic lineage are thought to be among the first cells infected after mucosal exposure to HIV. In this study, we have identified the presence of multiple chemokine receptors on dendritic cells (DC) that may function as coreceptors for HIV entry. DC effectively used CCR5 for entry of macrophage (M)-tropic isolates. CCR3, the eotaxin receptor, initially identified on eosinophils, is expressed on DC and may be used as an entry coreceptor by certain dual-tropic strains. CXCR4 was not expressed on DC, although SDF-1 induced a calcium flux and DC could be infected by T cell line (T)-tropic HIV. Our findings provide evidence for the presence of a non-CXCR4 SDF-1 receptor on DC that is used mainly by T-tropic strains of HIV. DC from individuals homozygous for a 32-bp deletion of the CCR5 gene are also infectable with M-tropic strains of HIV-1, and this infection is inhibited by stromal cell-derived factor (SDF)1, suggesting that this receptor can also be used by M-tropic HIV for entry. Delineation of the spectrum of coreceptor usage on DC may offer new approaches to interfere with the initiation and propagation of HIV infection.