Abstract: CD40 activating proteins comprising recombinant proteins with CD40 agonist antibodies or their antigen-binding fragments fused or linked to CD40 ligand are provided. The CD40 activating proteins may further comprise at least one antigen. Uses for the CD40 activating proteins include inducing immune responses directed to delivered antigens such as viral or cancer antigens. Properties of the CD40 activating protein may include the ability to induce proliferation of B cells or secretion of cytokines, such as IL-6, IL-12 and/or IL-15.

Abstract: Sarbecoviruses (lineage B of genus Betacoronavirus) have caused two major outbreaks during the past two decades: SARS-CoV in 2003, and SARS-CoV-2 from 2019. SARS-CoV-2 vaccines will be essential to reduce morbidity and mortality. Therefore, universal vaccines against this class of viruses are key to ending the current pandemic, but also for preventing additional emergent variations and future outbreaks of SARS-like viruses that are continuously found from nature reservoirs. Now, the inventors produced an antibody that is directed against a surface antigen (i.e., CD40) of an antigen presenting cell (i.e., dendritic cell) wherein the heavy chain is conjugated or fused to a protein N polypeptide of SAR-CoV-2 and the light chain is fused to a RBD polypeptide. In particular, the inventors show that said antibody could elicit immune responses against Sarbecoviruses.

Abstract: Chlamydiae are intracellular bacterial pathogens responsible for a variety of infections. The inventors produced an antibody that is directed against a surface antigen (i.e., CD40) of an antigen presenting cell (i.e., dendritic cell) wherein the heavy chain and/or light chain is conjugated to the MOMP VS4 domain of Chlamydia trachomatis for its use as vaccine.

Abstract: Chlamydiae are intracellular bacterial pathogens responsible for a variety of infections. The inventors have set up candidate vaccines against Chlamydia trachomatis. In particular, the inventors have identified specific epitopes to be included in vaccine candidates thanks to in silico analysis of the amino-acid sequence of these proteins to map predicted MHC-I and -II epitopes by online software (NetMHC-4.0 and NetMHCII-2.3) and peptide binding prediction software. B cell epitopes were also mapped using online software (BepiPred-2.0 and Discotope). Finally, the inventors have generated some specific CD40 or Langerin antibodies comprising one or more identified epitope(s) of the present invention and that are suitable for vaccine purposes. Therefore, the present invention relates to Chlamydia trachomatis (Ct) antigenic polypeptides and uses thereof for vaccine purposes.

Abstract: SARS-CoV-2 vaccines will be essential to reduce morbidity and mortality. The inventors produced an antibody that is directed against a surface antigen (i.e. CD40) of an antigen presenting cell (i.e. dendritic cell) wherein the heavy chain was conjugated to the receptor-binding domain of the Sars-Cov-2 spike protein for its use as vaccine. In particular, the inventors show that said vaccine induces circulating Ab-secreting hu-B cells, elicits S-specific IgG+ hu-B cells, elicits the expansion of central memory CD4+ hu-T cells and the emergence of effector memory CD4+ T cells, elicits the expansion of central memory CD8+ hu-T cells at and the emergence of effector memory CD8+ T cells at and finally induces Stem-cell like memory hu-CD8+ T cells.

Abstract: The present disclosure provides polypeptides derived from SARS-CoV-2 which have therapeutic use. One such polypeptide is a polypeptide, referred to as “Npep2,” is derived from the SARS-CoV-2 protein N and has at least 50 consecutive amino acids of the amino acid sequence having at least 90% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 of SEQ ID NO:2. Further described are conjugates wherein a heterologous polypeptide is conjugated or fused to Npep2. The present disclosure further provides vaccines employing the polypeptides, polynucleotides encoding the polypeptides, and methods of vaccinating subjects against SARS-CoV-2 by administering a therapeutically effective amount of one or more of the polypeptides.

Abstract: The invention relates to antibodies against human CD39 and use thereof for inhibiting T regulatory cells (Treg) activity. More particularly CD39 antibodies may be used for the treatment or prevention of cancers and infectious diseases.

Abstract: The disclosure relates to the field of OX40 activating proteins. More specifically, it is disclosed herein recombinant proteins with OX40 agonist antibodies or their antigen-binding fragments fused or linked to OX40 ligand. Also disclosed is the advantageous use of such OX40 activating proteins, in particular for inducing immune responses directed to delivered antigens such as viral or cancer antigens, and/or for treating cancer.

Abstract: The inventors now provide novel IL-15/IL-15 receptor alpha (IL-15R?) fusion proteins. Furthermore, as a complement to anti-PD-1 therapy, the inventors developed a series of anti-PD-1/IL-15/IL-15 receptor alpha (IL-15R?) immunocytokines that are able to simultaneously target multiple steps in the immune activation process. The development of said immunocytokines provides the potential benefits associated with anti-PD-1 antibodies and IL-15 administered individually with several distinct advantages. These include a significantly extended in vivo half-life relative to the IL-15 therapy, administration of a pre-formed IL-15/IL-15R? complex that would preclude the need for IL-15R? trans-presentation, high activity leading to a low target therapeutic dose and targeted delivery of IL-15 to regions with high PD-1 cells that will limit off-target adverse events.

Abstract: Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease in which the primary abnormality appears to affect the pilosebaceous-apocrine unit. Here, inventors' objective was to characterize the molecular mechanisms involved in the pro-inflammatory phenotype of HS-ORS cells. Transcriptomic analyses of HS-ORS cells demonstrated dysregulation of genes involved in cell proliferation and differentiation, as well as upregulation of the DNA damage response (DDR) and IFN signature. The inventors identified abnormalities in the HF-SC compartment from patients with HS, including high counts of proliferating progenitor cells and loss of quiescent bulge stem cells. Fork progression analysis revealed replicative stress responsible for ATR-CHK1 pathway activation. Accumulation of ssDNA and micronuclei in the cytosol of HS-ORS cells was found to contribute to STING activation via the DNA sensor IF116, inducing IFN synthesis independently of cGAS.

Abstract: The disclosure relates to the field of CD40 activating proteins. More specifically, it is disclosed herein recombinant proteins with CD40 agonist antibodies or their antigen-binding fragments fused or linked to CD40 ligand. Also disclosed is the advantageous use of such CD40 activating proteins, in particular for inducing immune responses directed to delivered antigens such as viral or cancer antigens.

Abstract: Septic shock is the leading cause of death in intensive care units. Previous studies have highlighted the immunosuppressive protein GILZ (glucocorticoid-induced leucine zipper) as a regulator of innate and adaptive immune responses. To go deeper in the understanding of GILZ protective role during sepsis, the inventors studied in vivo the consequences of a targeted overexpression of GILZ in monocytes and macrophages (M/M) in animal models of sepsis. In addition, they monitored the expression of GILZ in M/M of both patients with septic shock and septic mice. In particular, the inventors show that the overexpression of GILZ limited to M/M leads to an increase survival rate in mice with CLP-induced sepsis. These results provided new evidence for a central role of GILZ in M/M on the pathophysiology of septic shock, and pinpoint the fact that GILZ would be suitable for predicting survival time of patient suffering from sepsis.

Abstract: Methods and compositions are provided that can be used to vaccinate against and treat HIV. Specifically contemplated are vaccine compositions and methods of using these compositions treat HIV in patients. Aspects of the disclosure relate to an anti-CD40 antibody-HIV antigen fusion protein comprising (i) an anti-CD40 heavy chain (HCD40)-HIV antigen (Ag) fusion protein comprising the formula: HCD40-Ag, wherein Ag is a polypeptide with at least 80% sequence identity to SEQ ID NO:1; and (ii) an anti-CD40 light chain (LCD40).

Abstract: The present invention includes compositions and methods for the expression, secretion and use of novel compositions for use as, e.g., vaccines and antigen delivery vectors, to delivery antigens to antigen presenting cells. In one embodiment, the vector is an anti-CD40 antibody, or fragments thereof, and one or more antigenic peptides linked to the anti-CD40 antibody or fragments thereof, including humanized antibodies.

Abstract: The present invention includes compositions and methods for the expression, secretion and use of novel compositions for use as, e.g., vaccines and antigen delivery vectors, to delivery antigens to antigen presenting cells. In one embodiment, the vector is an anti-CD40 antibody, or fragments thereof, and one or more antigenic peptides linked to the anti-CD40 antibody or fragments thereof, including humanized antibodies.

Abstract: The invention relates to antibodies against human CD39 and use thereof for inhibiting T regulatory cells (Treg) activity. More particularly CD39 antibodies may be used for the treatment or prevention of cancers and infectious diseases.

Abstract: Methods and compositions are provided that can be used to vaccinate against and treat HIV. Specifically contemplated are vaccine compositions and methods of using these compositions treat HIV in patients. Aspects of the disclosure relate to an anti-CD40 antibody-HIV antigen fusion protein comprising (i) an anti-CD40 heavy chain (HCD40)-HIV antigen (Ag) fusion protein comprising the formula: HCD40-Ag, wherein Ag is a polypeptide with at least 80% sequence identity to SEQ ID NO:1; and (ii) an anti-CD40 light chain (LCD40).

Abstract: The invention provides diagnostic markers of immunosenescence and methods of identifying individuals with impaired immune function based on the expression level of a combination of such markers in a biological sample obtained from said individual. Such combination of markers is useful for determining the susceptibility to nosocomial infections of an individual. Such combination of markers is also useful for predicting whether an individual will respond to active vaccination and become protected against recurring diseases.

Abstract: Methods and compositions are provided that can be used to vaccinate against and treat HIV. Specifically contemplated are vaccine compositions and methods of using these compositions treat HIV in patients. Aspects of the disclosure relate to an anti-CD40 antibody-HIV antigen fusion protein comprising (i) an anti-CD40 heavy chain (HCD40)-HIV antigen (Ag) fusion protein comprising the formula: HCD40-Ag, wherein Ag is a polypeptide with at least 80% sequence identity to SEQ ID NO:1; and (ii) an anti-CD40 light chain (LCD40).

Abstract: The invention relates to antibodies against human CD39 and use thereof for inhibiting T regulatory cells (Treg) activity. More particularly CD39 antibodies may be used for the treatment or prevention of cancers and infectious diseases.