Development and Application of an Assay to Evaluate the Anti-Parasitic Effect of Humoral Responses against .

Mounting a balanced and robust humoral immune response is of utmost importance for reducing the infectivity of . While the role of such a response in controlling the infection is well known, there is a lack of tools that can be used to quickly evaluate it. We developed a serum parasite inhibition assay (to evaluate changes in the parasite infection after exposing infective trypomastigotes to serum samples from infected patients).

Computer-Aided Analysis of West Sub-Saharan Africa Snakes Venom towards the Design of Epitope-Based Poly-Specific Antivenoms.

Snakebite envenomation is a neglected tropical disease that causes over 100,000 deaths each year. The only effective treatment consists of antivenoms derived from animal sera, but these have been deemed with highly variable potency and are usually inaccessible and too costly for victims. The production of antivenoms by venom-independent techniques, such as the immunization with multi-epitope constructs, could circumvent those drawbacks.

IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria.

The Plasmodium falciparum erythrocyte-membrane-protein-1 (PF3D7_1150400/PF11_0521) contains both domain cassette DC13 and DBLβ3 domain binding to EPCR and ICAM-1 receptors, respectively. This type of PfEMP1 proteins with dual binding specificity mediate specific interactions with brain micro-vessels endothelium leading to the development of cerebral malaria (CM). Using plasma collected from children at time of hospital admission and after 30 days, we study an acquisition of IgG response to PF3D7_1150400/PF11_0521 DC13 and DBLβ3_D4 recombinant constructs, and five peptides located within these constructs, specifically in DBLα1.

Design of an Epitope-Based Vaccine Ensemble for Animal Trypanosomiasis by Computational Methods.

African animal trypanosomiasis is caused by vector-transmitted parasites of the genus . and are predominant in Africa; and in America and Asia. They have in common an extracellular lifestyle and livestock tropism, which provokes huge economic losses in regions where vectors are endemic.

Compression of Vectors for Small Interfering RNAs Delivery: Toward Oral Administration of siRNA Lipoplexes in Tablet Forms.

Currently, most nonviral nucleic acid vectors are in the form of colloidal suspensions administered primarily parenterally. This type of formulation and the mode of administration impose strong constraints such as the size of the administered vectors or the production of sterile preparations. The tablet form provides access to easy oral administration, well accepted by patients; As regards nucleic acid vectors, a dry form represents an advance in terms of stability.

Hepatic stellate cell hypertrophy is associated with metabolic liver fibrosis.

Hepatic fibrosis is a major consequence of chronic liver disease such as non-alcoholic steatohepatitis which is undergoing a dramatic evolution given the obesity progression worldwide, and has no treatment to date. Hepatic stellate cells (HSCs) play a key role in the fibrosis process, because in chronic liver damage, they transdifferentiate from a "quiescent" to an "activated" phenotype responsible for most the collagen deposition in liver tissue. Here, using a diet-induced liver fibrosis murine model (choline-deficient amino acid-defined, high fat diet), we characterized a specific population of HSCs organized as clusters presenting simultaneously hypertrophy of retinoid droplets, quiescent and activated HSC markers.

Corrigendum: Design of an Epitope-Based Vaccine Ensemble for Chagas Disease.

[This corrects the article DOI: 10.3389/fimmu.2019.

Targeting endothelial thioredoxin-interacting protein (TXNIP) protects from metabolic disorder-related impairment of vascular function and post-ischemic revascularisation.

Introduction: Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biological functions, the contribution of endothelial TXNIP has not been well-defined in regards to endothelial and vascular function or in post-ischemic revascularisation. We postulated that inhibition of endothelial TXNIP with siRNA or in a Cre-LoxP system could be involved in protection from high fat, high protein, low carbohydrate (HFHPLC) diet-induced oxidative stress and endothelial dysfunction, leading to vascular damage and impaired revascularisation in vivo.

Methods And Results: To investigate the role of endothelial TXNIP, the TXNIP gene was deleted in endothelial cells using anti-TXNIP siRNA treatment or the Cre-LoxP system.

Design of an Epitope-Based Vaccine Ensemble for Chagas Disease.

infection causes Chagas disease, which affects 7 million people worldwide. Two drugs are available to treat it: benznidazole and nifurtimox. Although both are efficacious against the acute stage of the disease, this is usually asymptomatic and goes undiagnosed and untreated.

Modifying internal organization and surface morphology of siRNA lipoplexes by sodium alginate addition for efficient siRNA delivery.

Vectorized small interfering RNAs (siRNAs) are widely used to induce specific mRNA degradation in the intracellular compartment of eukaryotic cells. Recently, we developed efficient cationic lipid-based siRNA vectors (siRNA lipoplexes or siLex) containing sodium alginate (Nalg-siLex) with superior efficiency and stability properties than siLex. In this study, we assessed the physicochemical and some biological properties of Nalg-siLex compared to siLex.

Cationic lipids as one-component vaccine adjuvants: A promising alternative to alum.

Effective vaccine formulations consist of several components: an antigen carrier, the antigen, a stimulator of cellular immunity such as a Toll-like Receptors (TLRs) ligand, and a stimulator of humoral response such as an inflammasome activator. Here, we investigated the immunostimulatory and adjuvant properties of lipopolyamines, cationic lipids used as gene carriers. We identified new lipopolyamines able to activate both TLR2 and TLR4 and showed that lipopolyamines interact with TLRs via a mechanism different from the one used by bacterial ligands, activating a strong type-I IFN response, pro-inflammatory cytokines and IL-1β secretion.

Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biologic functions, the contribution of endothelial TXNIP has not been well defined. To investigate the endothelial function of TXNIP, we generated a TXNIP knockout mouse on the Cdh5-cre background (TXNIP cdh5). Control (TXNIP) and TXNIP cdh5 mice were fed a high protein-low carbohydrate (HP-LC) diet for 3 mo to induce metabolic stress.

Analysis of the evolution of the detection limits of electrochemical nucleic acid biosensors II.

This critical review of electrochemical biosensors allowing direct detection of nucleic acid targets reports on different transduction pathways and their latest breakthroughs. A classification of the various strategies based on the nature of the electrochemical transduction is established to emphasize the efficiency of each of them. It provides an overall picture of the detection limit of the various approaches developed during the last two decades.

The absorption enhancer sodium deoxycholate promotes high gene transfer in skeletal muscles.

Gene delivery to skeletal muscle is a promising strategy for the treatment of muscle disorders and for the systemic secretion of therapeutic proteins. In addition, muscle is an attractive target tissue because it is easily accessible. However, very few synthetic vectors proved capable of surpassing naked DNA mediated muscle gene transfer.

Lipoplexes Strengthened by Anionic Polymers: Easy Preparation of Highly Effective siRNA Vectors Based on Cationic Lipids and Anionic Polymers.

RNA interference is an invaluable tool in biology to specifically silence a given gene. Synthetic duplexes of RNA oligonucleotides are widely used to induce mRNA degradation in cultured cells or in whole organisms. They have to be vectorized to reach their target site.

Characterization of an A-kinase anchoring protein-like suggests an alternative way of PKA anchoring in Plasmodium falciparum.

Background: The asexual intra-erythrocytic multiplication of the malaria parasite Plasmodium falciparum is regulated by various molecular mechanisms. In eukaryotic cells, protein kinases are known to play key roles in cell cycle regulation and signaling pathways. The activity of cAMP-dependent protein kinase (PKA) depends on A-kinase anchoring proteins (AKAPs) through protein interactions.

Inhibition of the myostatin/Smad signaling pathway by short decorin-derived peptides.

Myostatin, also known as growth differentiation factor 8, is a member of the transforming growth factor-beta superfamily that has been shown to play a key role in the regulation of the skeletal muscle mass. Indeed, while myostatin deletion or loss of function induces muscle hypertrophy, its overexpression or systemic administration causes muscle atrophy. Since myostatin blockade is effective in increasing skeletal muscle mass, myostatin inhibitors have been actively sought after.

Differential adhesion-inhibitory patterns of antibodies raised against two major variants of the NTS-DBL2X region of VAR2CSA.

Background: VAR2CSA is a large polymorphic Plasmodium falciparum protein expressed on infected erythrocytes (IE) that allows their binding in the placenta, thus precipitating placental malaria (PM). The N-terminal part of VAR2CSA that contains the binding site to placental chondroitin sulfate A (CSA) is currently recognized as the most attractive region for vaccine development. An ultimate challenge is to define epitopes in this region that induce a broad cross-reactive adhesion inhibitory antibody response.

DNA electroporation in rabbits as a method for generation of high-titer neutralizing antisera: examples of the botulinum toxins types A, B, and E.

Raising high titer antibodies in animals is usually performed by protein immunization, which requires the long and sometimes difficult step of production of the recombinant protein. DNA immunization is an alternative to recombinant proteins, only requiring the building of an eukaryotic expression plasmid. Thanks to efficient DNA delivery techniques such as in vivo electroporation, DNA vaccination has proven useful the last few years.

Reduced in vitro and in vivo toxicity of siRNA-lipoplexes with addition of polyglutamate.

We previously designed a new siRNA vector that efficiently silences genes in vitro and in vivo. The vector originality is based on the fact that, in addition to the siRNA molecule, it contains two components: 1) a cationic liposome that auto-associates with the siRNA to form particles called "lipoplexes" and, 2) an anionic polymer which enhances the lipoplex's efficiency. This anionic polymer can be a nucleic acid, a polypeptide or a polysaccharide.

First-trimester Plasmodium falciparum infections display a typical "placental" phenotype.

Background: Plasmodium falciparum-infected erythrocytes (IEs) adhere to host cell receptors, allowing parasites to sequester into deep vascular beds of various organs. This defining phenomenon of malaria pathogenesis is key to the severe clinical complications associated with cerebral and placental malaria. The principal ligand associated with the binding to chondroitin sulfate A (CSA) that allows placental sequestration of IEs is a P.

Electroporation-mediated genetic vaccination for antigen mapping: application to Plasmodium falciparum VAR2CSA protein.

Genetic vaccination, consisting in delivering a genetically engineered plasmid DNA by a non-viral vector or technique into a tissue, is currently of great interest. New delivery technique including DNA transfer by electroporation recently greatly improved the potency of this concept. Because it avoids the step of producing a recombinant protein, it is particularly of use in studying the immunogenic properties of large proteins.