Abstract: The present invention relates to an isolated microorganism belonging to the genus Mycobacterium, characterized in that it comprises inactivating the gene Rv0757 that confers a PhoP? phenotype and inactivating a second gene that prevents the production of DIM (DIM-phenotype). Additionally, the present invention comprises the use of said microorganism for producing a vaccine for immunizing against or preventing tuberculosis.

Abstract: The present invention provides novel n-alkenyl glycosides and glycoconjugates, n-alkyl glycoamino acids, and methods for the synthesis thereof. In another aspect, the present invention provides novel clustered glycopeptides and methods for the synthesis thereof. In still another aspect, the present invention provides methods for the treatment of cancer, preferably for the prevention of recurrence of cancer, and methods for inducing antibodies in a subject, comprising administering to a subject in need, an effective amount of any of the inventive glycoconjugates as disclosed herein.

Abstract: The present invention relates to the provision of novel immunogens comprising an antigenic PCSK9 peptide containing a phosphorylation site (with or without phosphorylation of the site) linked to an immunogenic carrier for the prevention, treatment or alleviation of PCSK9-mediated disorders. The invention further relates to methods for production of these medicaments, immunogenic compositions and pharmaceutical compositions thereof and their use in medicine.

Abstract: Methods for synthesis and manufacture of polysaccharide-protein conjugate vaccines at high yield are provided. The methods involve reaction of a hydrazide group on one reactant with an aldehyde or cyanate ester group on the other reactant. The reaction proceeds rapidly with a high conjugation efficiency, such that a simplified purification process can be employed to separate the conjugate product from the unconjugated protein and polysaccharide and other small molecule by-products.

Abstract: The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis. In particular, the present invention provides novel methods and compositions for eliciting a highly specific and highly effective immune response in an organism, but particularly within an animal, particularly a mammal or a human, which is capable of preventing or alleviating amyloidosis, or the symptoms associated with amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer's Disease (AD), including diseases or conditions characterized by a loss of cognitive memory capacity such as, for example, mild cognitive impairment (MCI).

Abstract: The present invention relates to a conjugate of a protein or peptide with a polyethylene glycol derivative having catechol, wherein the protein or peptide is mono-PEGylated at the N-terminal with the polyethylene glycol derivative, and to a preparation method thereof. According to the invention, the catechol-PEG derivative can be site-specifically conjugated with the N-terminal amine group of a protein or peptide, so that a homogeneous polyethylene glycol-protein or -peptide conjugate can be obtained in high yield. Unlike a prior art conjugate, the conjugate obtained according to the invention allows the decrease in the activity of the protein to be minimized without chemically modifying the protein, and thus the conjugate has an excellent pharmacological effect. Also, because the conjugate is homogeneous, the process for preparing the conjugate can be simplified. Moreover, the conjugate has uniform biological efficacy in vivo and shows strong resistance to hydrolysis and thus a long in vivo duration time.

Abstract: The present invention relates to interferon-?2b modified with Y-shaped branched polyethylene glycol (PEG) at a single Lys residue and the preparation thereof. The peglated IFN-?2b can be used for the preparation of a medicament for treating a disease, e.g. viral infections such as Hepatitis C.

Abstract: The present invention relates to interferon (IFN)-?2a modified at a specific Lys residue with Y-shaped branched polyethylene glycol (PEG) derivative and the preparation thereof, as well as the use of the prepared IFN-?2a modified by PEG at a single amino acid residue in medicines.

Abstract: Chimeric molecules that contain at least one pathogen-detection domain and at least one effector domain, and their methods of use in preventing or treating a pathogen infection in a cell or organism are described. The pathogen-detection domain and effector domain of the chimeric molecules are domains not typically found in nature to be associated together. Agents are also described herein having at least one pathogen-interacting molecular structure and at least one effector-mediating molecular structure, the agent being one that is non-naturally-occurring in a cell. The methods of prevention and treatment described herein are effective for a broad spectrum of pathogens and exhibit little or no toxic side-effects. Assays for the detection of a pathogen, pathogen component, or product produced or induced by a pathogen, are also provided.

Abstract: The methods include selectively reducing or expanding T cells according to the antigenic specificity of the T cells. Therefore, the present invention can be used to reduce or eliminate pathogenic T cells that recognize autoantigens, such as beta cell specific T cells. As such, the present invention can be used to prevent, treat or ameliorate autoimmune diseases such as IDDM. Furthermore, the present invention can be used to expand desirable T cells, such as anti-pathogenic T cells to prevent, treat and/or ameliorate autoimmune diseases.

Abstract: Lipid conjugates for enhanced delivery of cargo to the lymph nodes are disclosed. The lipid conjugates typically include three domains: a lipophilic domain that binds to albumin, a polar block domain, and a cargo such as a molecular adjuvant or immunostimulatory compound (such as an oligonucleotide) or antigenic peptide. Depending on the cargo, the length and compositions of the polar block can be tailored to push the equilibrium toward albumin binding, stable micelle formation, or cell insertion. The conjugates can be administered to a subject, for example, a subject with cancer or an infection, to induce or enhance a robust immune response in the subject.

Abstract: The present invention is directed to an inventive composition or vaccine composition comprising a) an adjuvant component comprising or consisting of at least one immunostimulatory nucleic acid sequence, complexed with a complexing agent; b) an antigen, preferably a protein or peptide antigen and/or a nucleic acid sequence encoding said antigen; and c) a carrier molecule for combined packaging the adjuvant component and the antigen. The present invention is also directed to the first medical use of such an inventive composition or vaccine composition and to the second medical use of such an inventive composition or vaccine composition or components thereof for the treatment of diseases, such as infectious or cancer or tumour diseases as defined herein. The present invention furthermore discloses kits comprising such a composition or vaccine composition.

Abstract: Provided are bivalent immunogenic composition against morphine-heroin addiction comprising a carrier protein (“CP”) and a morphinic product, wherein the CP and the morphinic product are connected by a spacer-linker arm having a total molecular size of 16-21 ?, and methods of using the same.

Abstract: Disclosed are fusion proteins comprising a biologically active molecule and an immunoglobulin (Ig) Fc domain which is linked to the biologically active molecule. The Fc domain is a hybrid human Fc domain of (i) IgG1, IgG2 or IgG4 or (ii) IgG4 and IgD. The hybrid Fc is useful as a carrier of biologically active molecules.

Abstract: Three conjugation methods for use with the capsular saccharide of Streptococcus agalactiae. In the first method, reductive animation of oxidized sialic acid residue side chains is used, but the aldehyde groups are first aminated, and then the amine is coupled to a carrier via a linker. In the second method, sialic acid residues and/or N-acetyl-glucosamine residues are de-N-acetylated to give amine groups, and the amine groups are coupled to a carrier protein via a linker. In the third method, linkage is via galactose residues in the capsular saccharide rather than sialic acid residues, which can conveniently be achieved using galactose oxidase.

Abstract: Methods for making an immunogenic conjugate that includes a hapten or an antigen covalently linked to a carrier. The methods include reacting a first agent with a dihydrazide resulting in a hydrazine-modified first agent, wherein the first agent is a hapten, an antigen or a carrier; reacting a second agent with a benzaldehyde compound resulting in a benzaldehyde-modified second agent, wherein the second agent is a hapten, an antigen or a carrier, provided that the first agent or the second agent is a carrier; and reacting the hydrazine-modified first agent with the benzaldehyde-modified second agent resulting in an immunogenic conjugate comprising a hapten or an antigen covalently linked to a carrier via a hydrazone linkage.

Abstract: Disclosed herein are stable complexes including an MHC class I or MHC class II recombinant T cell receptor ligand RTL polypeptide covalently linked to an antigenic determinant by a disulfide bond. Also disclosed are methods of making such compositions and methods of use, for example to treat or inhibit a disorder, for example, an autoimmune disorder.

Abstract: The present invention relates to the provision of novel immunogens comprising an antigenic IgE peptide preferably linked to an immunogenic carrier for the prevention, treatment or alleviation of IgE-mediated disorders. The invention further relates to methods for production of these medicaments, immunogenic compositions and pharmaceutical compositing thereof and their use in medicine.

Abstract: Compositions, methods, and vaccines that may stimulate the immune system and that may be used for treating malignancies associated with overexpression of the HER-2 protein are provided. Such compositions include epitopes of the HER-2 proteins.

Abstract: The invention provides TLR agonists and conjugates thereof useful in vaccines and to prevent, inhibit or treat a variety of disorders including pathogen infection and asthma.

Abstract: The present invention refers to the preparation of adenine derivative active esters of formula (I) and use thereof for the preparation of stable conjugates between adenine derivative and allergenic proteins having general structure (II) for the modulation of TH2 response in allergic diseases.(I, II).

Abstract: Disclosed are immunogenic conjugates which elicit an immune response to Plasmodium proteins. In particular examples, the Plasmodium proteins include sexual stage surface proteins, circumsporozoite protein (CSP), or immunogenic portions of CSP. Also provided herein are immunogenic compositions including one or more of the disclosed immunogenic conjugates and a pharmaceutically acceptable carrier. Further provided is a method of eliciting an immune response to Plasmodium in a subject, comprising administering to the subject an immunogenic composition disclosed herein.

Abstract: Methods for producing an immune response to Mycobacterium tuberculosis (Mtb) are disclosed herein. In several examples, the immune response is a protective immune response. In additional embodiments, methods are disclosed for preventing an infection with Mtb, or treating an infection with Mtb. Pharmaceutical compositions for the prevention and/or treatment of tuberculosis are also disclosed.

Abstract: Featured is T cell receptor complexes designed to redirect the immune system against various diseases. The T cell receptor complexes of the invention have been engineered to recognize target antigen in a functionally bispecific nature. Fusion protein complexes and protein conjugate complexes are comprised of high affinity antigen-specific TCR and biologically active proteins and/or effector molecules. Also featured is methods of production of T cell receptor fusion and conjugate complexes as well as therapeutic compositions for use of the complexes.

Abstract: Nanoparticles for providing immune responses for the treatment or prophylaxis of infection by infectious agents such as viruses, parasites, bacteria, prions and fungi are described which comprises a core including metal and/or semiconductor atoms, wherein the core is covalently linked to a plurality of ligands, the ligands including a carbohydrate residue capable of stimulating an innate immune response, a T cell helper peptide and a danger signal. This platform may then be adapted by including one or more further ligands capable of producing a specific response to a target infectious agent.

Abstract: Forms of GAS25 (streptolysin O) which are not toxic but which still maintain the ability to induce protection against S. pyogenes are useful in vaccine compositions to induce protection against S. pyogenes.

Abstract: A polypeptide inhibiting binding between a vascular endothelial growth factor and a vascular endothelial growth factor receptor, a fusion protein including the same, and a method of preparing the fusion protein are disclosed.

Abstract: The present invention relates to new lipopeptide- and lipoprotein molecules and lipopeptide- and lipoprotein-conjugates. In particular, the present invention relates to new lipopeptide- and lipoprotein molecules and lipopeptide- and lipoprotein-conjugates comprising a lipid-containing moiety representing an adjuvant moiety, a peptide or protein moiety whereby said peptide or protein moiety represents at least one antigenic structure, the antigen-moiety, and, optionally, a conjugate moiety, preferably a monodisperse polyethyleneglycol unit. Said compounds are particularly useful for therapeutic or prophylactic vaccination by mucosal or systemic administration, preferably mucosal and systemic vaccination. That is, the present invention relates in another aspect to pharmaceutical compositions comprising the compounds according to the present invention, in particular, said pharmaceutical compositions are vaccines.

Abstract: A stable immunogenic product for the induction of antibodies against one or more antigenic proteins in a subject, characterized in that it comprises proteinaceous immunogenic heterocomplexes which are formed by associations between (i) antigenic protein molecules and (ii) proteinaceous carrier molecules and in that less than 40% of the antigenic proteins (i) are linked to the proteinaceous carrier molecules (ii) by a covalent bond.

Abstract: The present disclosure relates to vaccine compositions, particularly KLH-peptide conjugates, and methods of making such compositions. The present disclosure further relates to methods of reducing abnormal cell growth using the composistions described herein.

Abstract: The invention provides TLR agonists and conjugates thereof useful in vaccines and to prevent, inhibit or treat a variety of disorders including pathogen infection and asthma.

Abstract: The structural design, preparative methods and chemical composition of two structural formulations of bivalent vaccines against morphine-heroin addiction (morphine-6-hemisuccinyl-EDC-TFCS-tetanus toxoid and 3-O-carboxymethylmorphine-EDC-TFCS-tetanus toxoid), are disclosed. These vaccines are suitable for human use in which they are capable of triggering the synthesis of polyclonal antibodies against morphine opiate and its structural analogue, heroin, through the repeated in vivo administration of these formulations, in active vaccination protocols, in pre-clinical studies in rodents. The active vaccination paradigm through which these immunogens trigger a humoral immune response consolidated with a long-term immunological memory, characterized by the presence of high titers of specific antibodies against these two drugs of abuse, is also disclosed.

Abstract: The present application discloses an improved method for conducting saccharide—protein conjugation reactions using carbodiimide condensation chemistry. Depending on the nature of the saccharide or protein carrier involved, the quality of the conjugate may be improved by adding one of the reaction components slowly to the reaction mixture. Immunogenic compositions are further provided comprising the saccharide-protein conjugates made by the methods disclosed.

Abstract: The present invention provides an immunogenic conjugate comprising biologically deacylated gram-negative bacterial moieties linked to D. discoideum proteinase 1, as well as novel subunits thereof, and methods of making and using the conjugates in vaccines to treat sepsis and other infectious complications.

Abstract: The present invention relates to an immunogenic composition comprising at least 2 different S. pneumoniae capsular saccharides, wherein one or more is/are selected from a first group consisting of serotypes 1, 3, 19A and 19F which is/are linked to a protein carrier(s) either directly or indirectly through a chemistry other than reductive amination, and one or more different saccharides is/are selected from a second group consisting of serotypes 4, 5, 6A, 6B, 7F, 9V, 14, 18C and 23F which is/are linked to a protein carrier(s) by reductive amination. Uses of such compositions are also disclosed.

Abstract: The present invention relates to three-branched PEG-G-CSF conjugate of general formula (1) in which the bonding ratio of three-branched polyethylene glycol (PEG) and G-CSF is 1:1 (mol/mol), wherein PEG has an average molecular weight of from 200 to 45,000 daltons; a pharmaceutical composition comprising the same, and a preparing method thereof.

Abstract: This application relates to peptide conjugates comprising peptides that suppress or otherwise inhibit an unwanted or undesirable immune response attached to lipid moieties, and methods for suppressing immune responses, including preventing, inhibiting, treating or decreasing unwanted or undesirable immune responses including autoimmune or allergic immune responses using these peptide conjugates.

Abstract: Methods are provided for the treatment of a retinal disorder or optic neuritis in a subject. In some embodiments, the methods include administering a therapeutically effective amount of an MHC molecule including covalently linked first, second, and third domains; wherein the first domain is an MHC class II ?1 domain and the second domain is an MHC class II ?1 domain, wherein the amino terminus of the ?1 domain is covalently linked to the carboxy terminus of the ?1 domain; or wherein the first domain is an MHC class I ?1 domain and the second domain is an MHC class I ?2 domain, wherein the amino terminus of the ?2 domain is covalently linked to the carboxy terminus of the ?1 domain; and wherein the third domain is covalently linked to the first domain and comprises a retinal antigen or an antigen of the central or peripheral nervous system.

Abstract: The present invention relates to the provision of novel immunogens comprising an antigenic IgE peptide preferably linked to an immunogenic carrier for the prevention, treatment or alleviation of IgE-mediated disorders. The invention further relates to methods for production of these medicaments, immunogenic compositions and pharmaceutical compositing thereof and their use in medicine.

Abstract: This invention relates to the field of vaccination and treatment or prevention diseases. In particular this invention relates to the treatment or prevention of diseases by inducing hapten-specific antibody responses in a vaccinated subject. The invention further provides a method for prevention or treatment of a disease by inducing hapten-specific antibodies in a subject comprising administering into said subject a composition comprising a virus-like particle of an RNA bacteriophage and at least one hapten linked thereto.

Abstract: Cell-permeable caPCNA-derived peptides and their variants serve as therapeutic compositions to reduce the proliferation of cancerous cells and also augment cytotoxic effects of chemotherapeutics.

Abstract: A polypeptide inhibiting binding between a vascular endothelial growth factor and a vascular endothelial growth factor receptor, a fusion protein including the same, and a method of preparing the fusion protein are disclosed.

Abstract: The invention provides immunomodulatory compounds and methods for immunomodulation of individuals using the immunomodulatory compounds.

Abstract: The invention relates to a product which comprises a C4bp domain of a non-mammalian origin, particularly SEQ ID NO:1, SEQ ID NO:23 or SEQ ID NO:37, or a variant thereof, and an antigen. The product is desirably in the form of a fusion protein. The chicken C4bp domain of SEQ ID NO:1 and SEQ ID NO:23 is also described. Antigens include monomeric antigens such as malarial and influenza antigens. The C4bp domain provides for assembly of multimeric complexes of the antigen, or mixtures thereof. The complexes are useful as vaccines.

Abstract: The present invention is related to methods and compositions that are capable of immediately immunizing a human or animal against any molecule or compound. The present invention comprises an immunity linker molecule with at least two sites; (1) a first binding site that binds to an immune system molecule in a human or animal that has been preimmunized against the first binding site, and (2) one or more second binding sites that bind specifically to a desired compound or molecule. The first binding site and the second binding site(s) are linked by a linker portion of the molecule.

Abstract: Methods for preparing complex multivalent immunogenic conjugates that include simultaneously reacting a plurality or immunogenic-distinct polysaccharides with at least one protein to make the complex multivalent immunogenic conjugates. The simultaneous reaction involves reaction of a hydrazide group on one reactant with an aldehyde or cyanate ester group on the other reactant.

Abstract: The present invention relates to the field of neisserial vaccine compositions, their manufacture, and the use of such compositions in medicine. More particularly it relates to processes of making novel engineered meningococcal strains which are more suitable for the production of neisserial, in particular meningococcal, outer-membrane vesicle (or bleb) vaccines. Advantageous processes and vaccine products are also described based on the use of novel LOS subunit or meningococcal outer-membrane vesicle (or bleb) vaccines which have been rendered safer and/or more effective for use in human subjects. In particular combinations of gene downregulations are described such as PorA and OpA, PorA and OpC, OpA and OpC, and PorA and OpA and OpC. Alternatively, or in addition, lgtB? is shown to be an optimal mutation for effectively and safely using L3 and/or L2 LOS in Neisseria vaccine compositions.

Abstract: Helicobacter pylori, one of the most common human pathogens, is associated with the development of human chronic gastritis, peptic ulcers and gastric cancer. The invention relates to a ?1,6-glucan-containing Helicobacter pylori compound comprising the structure of Formula (I): wherein R is a ?-DDHep-3-?-L-Fuc-3-?-GlcNAc trisaccharide substituted with an ?1,6-glucan linked to an ?1,3-DD-heptan, and wherein the last DD-Hep residue of ?1,3-DD-heptan is capped with ?-GlcNAc residue. Compositions comprising the compound, uses of the compound, and antibodies raised against the compound are also described.

Abstract: This invention relates to conjugates of the Vi polysaccharide of S. typhi with the carrier Pseudomonas aeruginosa recombinant exoprotein A (rEPA), and compositions thereof, and to methods of using of these conjugates and/or compositions thereof for eliciting an immunogenic response in humans, including responses which provide protection against, or reduce the severity of, S. typhi bacterial infections. The conjugates, and compositions thereof, are useful as vaccines to induce serum antibodies against S. typhi and are useful to prevent and/or treat illnesses caused by S. typhi.

Abstract: The invention provides TLR agonists and conjugates thereof useful in vaccines and to prevent, inhibit or treat a variety of disorders including pathogen infection and asthma.