Abstract: The present invention pertains to the field of protein engineering, and provides means for obtaining stable molecules that specifically bind to a target selected amongst a large variety of ligands families. In particular, the present invention provides methods for obtaining a molecule specifically binding to a target of interest, through a combinatorial mutation/selection approach with an OB-fold protein as a starting molecule. In particular, the target of interest can be of a different chemical nature form that of the native target of the OB-fold protein used as the starting molecule.

Abstract: Methods of treating acute and chronic inflammatory conditions, tissue transplant rejection, and/or organ transplant rejection comprising administering to a subject in need thereof a therapeutically effective amount of a pluripotent anti-inflammatory and metabolic modulators optionally in combination with one or more secondary therapeutic agents and pharmaceutical compositions thereof.

Abstract: Methods of treating sepsis induced acute brain dysfunction (SiBD), comprising administering a synaptic vesicle 2a and/or 2b binding chemical entity to a subject with sepsis. Methods of reducing sepsis mortality, comprising administering a synaptic vesicle 2a and/or 2b binding chemical entity to a subject with sepsis. In some embodiments the synaptic vesicle 2a and/or 2b binding chemical entity is a synaptic vesicle 2a and/or 2b modulator such as agonist, partial agonist, antagonist or partial antagonist. In some embodiments the synaptic vesicle 2a and/or 2b binding chemical entity is levetiracetam or a derivative or analogue of levetiracetam. In some embodiments the synaptic vesicle 2a binding chemical entity is levetiracetam.

Abstract: The present invention is directed to a Zika virus (ZIKV) chimeric polyepitope comprising non-structural proteins and its use in an immunogenic composition. The present invention provides means, in particular polynucleotides, vectors and cells expressing said chimeric polyepitope. The present invention also relates to a composition or a vaccine comprising at least one of said polyepitope, polynucleotide, vector or host cell for use in the prevention of a ZIKV infection in a human subject, or for use in the prevention of ZIKV and dengue virus (DENV) infections in a human subject.

Abstract: The invention provides methods of reducing development of mild cognitive impairment and/or learning disorders and/or memory disorders in a subject suspected to have or suffering from Alzheimer's disease (AD). In some embodiments, the methods comprise administering a therapeutically effective amount of a beta-2 nicotinic acetylcholine receptor (nAChR) antagonist and/or beta-2 nAChR negative allosteric modulator (NAM) to the subject over a therapeutic dosing period to thereby reduce the rate of development of mild cognitive impairment and/or learning disorders and/or memory disorders in the subject over the therapeutic dosing period.

Abstract: The application relates to means, which derive from TAL effectors and TALENs. The structure of the means of the application is especially adapted for partial or full deletion of at least one DNA tandem repeat, more particularly for partial or full deletion of at least one DNA tandem repeat in a double-stranded DNA, more particularly for partial or full deletion of at least one DNA tandem repeat, which is contained in a double-stranded DNA and, which forms a complex secondary structure, such as a hairpin, a triple helix or a tetraplex secondary structure. The means of the application are notably useful in the treatment and/or prevention and/or palliation of a disease or disorder involving at least one DNA tandem repeat, such as DM1, SCA8, SCA12, HDL2, SBMA, HD, DRPLA, SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, PSACH, DM2, SCA10, SPD1, OPMD, CCD, HPE5, HFG syndrome, BPES, EIEE1, FRAXA, FXTAS and FRAXE.

Abstract: The invention relates to mutant DNA polymerases of the Pol theta subfamily capable of performing non-templated nucleic acid extension, or of a functional fragment of such a polymerase, methods of producing these mutant DNA polymerases, kits and methods of using these mutant DNA polymerases.

Abstract: The invention relates to Plasmodium antigenic polypeptides identified through the use of a specifically devised functional immunization screening assay. In particular, the invention relates to antigenic polypeptides of malaria parasites wherein said antigenic polypeptides that exhibit a protective effect, especially that of eliciting a protective immune response in a host against challenge by Plasmodium sporozoites. The invention relates to a combination of compounds, comprising at least 2 distinct active ingredients wherein each active ingredient consists of an antigenic polypeptide of a Plasmodium parasite, a polynucleotide encoding the antigenic polypeptide, or a vector, in particular a viral vector, especially a lentiviral vector, expressing such antigenic polypeptide of a Plasmodium parasite, wherein one antigenic polypeptide is the circumsporozoite protein (CSP) or a polypeptidic derivative thereof and another antigenic polypeptide is either protein Ag40 (11-09) or protein Ag45 (11-10).

Abstract: The invention relates to Interleukin-2 (IL-2) variants for the prevention or treatment of immune disorders, including with no limitations allergic, autoimmune, chronic or acute inflammatory and infectious diseases; graft-versus-host disease; graft rejection and cancer. The invention also relates to the use of said IL-2 variants for the screening of anti-IL-2 antibodies with pro-T-effector or pro-T-regulatory cell activity.

Abstract: The present invention relates to the treatment of microbiome dysregulations. Said dysregulations may subsequently contribute to the development of several chronic diseases. Thus characterization of new post-biotic compounds inducing beneficial changes on host-microbiota interactions may be highly desirable. The inventors showed that Nlrp6 diurnally coordinates cyclical adaptation of the gut microbiota diversity to epithelial plasticity in response to a treatment with a Csnk2 inhibitor. The invention therefore relates to an inhibitor of Csnk2, for use in the treatment of microbiome dysregulations notably associated with circadian clock disruption. Said inhibitor may be selected among chemically synthesized or natural selective Csnk2 inhibitors such as flavones.

Abstract: Methods for diagnosing or treating immune disorders in a subject are provided. The methods are based on the detection or modulation of Refractory state Inducing Factor (RIF).

Abstract: The invention relates to the improvement of endonuclease-based antimicrobials by blocking DNA repair of double-strand break(s) (DSB(s)) in prokaryotic cells. In this respect, the invention especially concerns a method involving blocking DNA repair after a nucleic acid has been submitted to DSB, in particular by a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated programmable double-strand endonuclease. The invention particularly relates to the use of an exogenous molecule that inhibits DNA repair, preferably a protein that binds to the ends of the double-stranded break to block DSB repair. The invention also relates to vectors, particularly phagemids and plasmids, comprising nucleic acids encoding nucleases and Gam proteins, and a pharmaceutical composition and a product containing these vectors and their application.

Abstract: The invention relates a recombinant measles virus plasmid capable of expressing a human telomerase reverse transcriptase (hTERT) protein fused at N-terminus with a protein enhancing addressing of the hTERT protein to proteasome. The invention further relates to a vaccine comprising said plasmid or particles rescued therefrom, and uses thereof, especially in preventing or treating a tumor in a patient.

Abstract: The present invention relates to the field of muscle regeneration, and more particularly to the replenishment of the in vivo muscle stem cells pool. It more specifically relates to a 5-hydroxytryptamine B1 receptor-stimulating agent, and to a composition comprising said agent, for use as i) a promoter of satellite cells self-renewal and/or differentiation, and/or ii) an agent preventing and/or inhibiting the satellite cells pool exhaustion. The invention further encompasses therapeutic and screening methods.

Abstract: The invention is in the domain of delivery of molecules to brain cells across the blood-brain barrier. The invention relates to a novel polypeptide-based carrier that allows the efficient delivery of an effector peptide, to neuron cells across the blood-brain barrier, and to methods for the production and testing of such carrier, including a model for testing the capacity of such molecule to cross the blood-brain barrier and/or the toxicity of molecules on the blood brain barrier and/or the capacity of molecules that have crossed to target human brain cells (e/g. neurons, astrocytes and microglial cells).

Abstract: The present disclosure relates to a method of preventing or treating an infectious disease in a subject, comprising the step of administering to the subject an antagonist or expression inhibitor for a natural killer (NK) cell immune checkpoint molecule. The present disclosure also relates to the use of an antagonist or expression inhibitor for an NK cell immune checkpoint molecular and pharmaceutical compositions comprising the same in the treatment of infectious diseases.

Abstract: The application generally relates to olfaction as a biomarker, more particularly as a prognostic biomarker or biological predictor, of neurosensory disease or disorder and/or of neurocognitive disease or disorder, in subjects whose nervous system has been infected by an infectious agent, such as by a neurotropic virus, bacterium, protozoan parasite, fungus or prion, more particularly by a neurotropic virus.

Abstract: The invention relates to a method of predicting therapeutic responses to TNF blockers before anti-TNF therapy comprising analyzing immune parameters to selected stimuli in patients before therapy and its use for anti-TNF therapy. The invention relates also to a method of determining a predictive biomarker of response to anti-TNF therapy and to the use of the predictive biomarker obtained by the method.

Abstract: The application relates to means for diagnosing, predicting or monitoring Pneumocystis pneumonia (PCP). The means of the application are also suitable for determining or predicting the efficacy of a drug or treatment against PCP in a human patient. The means of involve the detection and/or quantification, more particularly the quantification, of the RNA transcripts of two different P. jirovecii mitochondrial genes. The first of said two P. jirovecii mitochondrial genes is the P. jirovecii gene, the sequence of which codes for the Cytb protein or the P. jirovecii mitochondrial Small Sub-Unit (mtSSU) gene. The second of said two P. jirovecii mitochondrial genes is a P. jirovecii gene, the sequence of which transcribes into a P. jirovecii ribosomal RNA, e.g., be the mitochondrial P. jirovecii Large Sub-Unit (mtLSU) gene.

Abstract: The success of anti-tumor immune responses requires effector T cells to infiltrate solid tumors, a process guided by chemokines. Herein, we demonstrate that in vivo post-translational processing of chemokines by dipeptidylpeptidase 4 (DPP4, also known as CD26) limits lymphocyte migration to sites of inflammation and tumors. Inhibition of DPP4 enzymatic activity enhanced tumor rejection by preserving biologically active CXCL10, and increasing trafficking into the tumor by lymphocytes expressing the counter-receptor CXCR3. Furthermore, DPP4 inhibition improved adjuvant-based immunotherapy, adoptive T cell transfer and checkpoint blockade. These findings provide the first direct in vivo evidence for controlling lymphocyte trafficking through CXCL10 cleavage and support the use of DPP4 inhibitors for stabilizing the biologically active form of chemokines as a strategy to enhance tumor immunotherapy.