Abstract: This disclosure provides a bispecific ligand directed toxin (BLT) that includes a diphtheria toxin (DT) molecule that has been mutated to create a DT molecule that induces less of an immune response than native diphtheria toxin. The deimmunized DT molecule is fused with targeting ligands to create a fusion protein that can selectively deliver the deimmunized DT to target cells to kill the target cells.

Abstract: Capsular saccharides derived from serogroups W135 and Y of Neisseria meningitidis have altered levels of O-acetylation at the 7 and 9 positions of their sialic acid residues, and can be used to make immunogenic compositions. Relative to unmodified native saccharides, derivatives of the invention are preferentially selected during conjugation to carrier proteins, and conjugates of the derivatives show improved immunogenicity compared to native polysaccharides.

Abstract: The present invention relates to a fermentation medium for cultivating Corynebacterium diphtheriae. The present invention also relates to the use of the fermentation medium in processes for obtaining diphtheria toxin from the Corynebacterium diphtheriae bacteria being cultivated and the preparation of vaccines using the diphtheria toxin obtained in the processes. The present invention further relates to a purification and detoxification processes specifically adapted for preparing a diphtheria toxoid for inclusion into a vaccine.

Abstract: The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

Abstract: The present invention relates to the provision of immunogens comprising an antigenic PCSK9 peptide 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 compositing thereof and their use in medicine.

Abstract: The present invention relates to methods and compositions of modified variants of diphtheria toxin (DT) that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome. One aspect of the present invention relates to a polypeptide toxophore from a modified DT, wherein the mutation is the substitution or deletion at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of native DT. Another aspect of the present invention relates to a fusion protein which comprises a modified DT and a non-DT fragment. Another aspect of the present invention relates to the use of modified DT for the treatment of cancer.

Abstract: Described are acellular pertussis (aP) vaccine compositions comprising Bordetella pertussis antigens pertussis toxoid (PT), filamentous hemagglutinin (FHA), and fimbriae types 2 and 3 (FIM), and optionally pertactin (PRN), wherein FIM is present in an amount of 12-100 ?g per human dose.

Abstract: The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of A? in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the amyloid deposit. The methods are useful for prophylactic and therapeutic treatment of Alzheimer's disease. Preferred agents including N-terminal fragments of A? and antibodies binding to the same.

Abstract: The present invention relates to the field of vaccines for protecting against tetanus, and in particular processes for the production of vaccines comprising tetanus toxoid adsorbed onto aluminium salts. Processes are provided whereby tetanus toxoid is absorbed onto aluminium salt adjuvant having defined characteristics for optimal results.

Abstract: The invention provides a diphtheria, tetanus and pertussis vaccine comprising a low dose of each of diphtheria toxoid (D), tetanus toxoid (T), pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (69K). The vaccine maintains an ability to prevent pertussis while showing exceptionally low reactogenicity. Combination vaccines comprising additional antigens are also provided.

Abstract: Provided herein are methods for generating dry vaccine powder formulations. Dry vaccine powder formulations can be used for intranasal delivery. Also provided are methods for stimulating local mucosal and systemic immunity by intranasal vaccine delivery.

Abstract: The present invention relates to a combination vaccine comprising a mixture of antigens for protection against diseases such as diphtheria, tetanus, acellular pertussis, and infections caused by Haemophilus influenzae and polio viruses. The present invention also relates to inclusion of antigens for protection against infections caused Hepatitis virus and other pathogens, such that administration of the vaccine can simultaneously immunize a subject against more than one pathogen. The invention in particular relates to a fully liquid stable combination vaccine comprising the antigens as indicated above and the methods for manufacturing the same.

Abstract: Present invention relates to vaccine formulations and adjuvants for use in e.g. compositions, thereby avoiding the phenomenon of Bell's palsy in a frequency above the natural occurance.

Abstract: Provided herein are methods for generating dry vaccine powder formulations. Dry vaccine powder formulations can be used for intranasal delivery. Also provided are methods for stimulating local mucosal and systemic immunity by intranasal vaccine delivery.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface and an immunostimulatory moiety. In some embodiments, the immunostimulatory moiety is an adjuvant. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

Abstract: The present invention is directed to pharmaceutical agents and compositions useful for the treatment and prevention of amyloid disease in a subject. The invention further relates to isolated antibodies that recognize a common conformational epitope of amyloidogenic proteins or peptides that are useful for the diagnosis, treatment, and prevention of amyloid disease.

Abstract: Methods for prevention, treatment or inhibition of the growth or metastasis of cancer cells in a subject are disclosed. One method comprises the step of administering to the subject a therapeutically effective amount of tumor associated antigen binding ligand-coated planetary ball milled (PBM) nanoparticles containing a cytotoxic agent.

Abstract: The present invention relates to immunogenic compositions comprising capsular polysaccharide or oligosaccharide of H. influenzae B (PRP) and methods of making such compositions.

Abstract: The invention relates to the discovery of novel soluble neutral active Hyaluronidase Glycoproteins (sHASEGPs), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. The invention further comprises sialated and pegylated form of a recombinant sHASEGP to enhance stability and serum pharmacokinetics over naturally occurring slaughterhouse enzymes. Further described are suitable formulations of a substantially purified recombinant sHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity.

Abstract: The present invention relates to methods and compositions of modified variants of diphtheria toxin (DT) that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome. One aspect of the present invention relates to a polypeptide toxophore from a modified DT, wherein the mutation is the substitution or deletion at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of native DT. Another aspect of the present invention relates to a fusion protein which comprises a modified DT and a non-DT fragment. Another aspect of the present invention relates to the use of modified DT for the treatment of cancer.

Abstract: The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of A? in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the amyloid deposit. The methods are useful for prophylactic and therapeutic treatment of Alzheimer's disease. Preferred agents including N-terminal fragments of A? and antibodies binding to the same.

Abstract: The present invention relates to the field of vaccines, and in particular vaccines comprising antigens of low isoelectric point at pH 7.0, in particular the capsular polysaccharide or oligosaccharide of H. influenzae B (PRP). Immunogenic compositions and methods of making such compositions are presented in which the PRP is surprisingly protected from immune interference by adding a polyanionic polymer (such as PLG-poly-L-glutamic acid) to the composition.

Abstract: The present invention relates to the use of live mycobacterium of the M. tuberculosis complex for preparing a medicament, wherein the function of the zmp1-gene is inactivated, pharmaceutical compositions prepared from such mycobacteria as well as a method for the treatment and/or prophylaxis of a disease or medical condition using said pharmaceutical composition.

Abstract: A Corynebacterium diphtheriae culture medium for the production of diphtheria toxin and methods for producing the toxin are provided. The medium is substantially free of animal-derived products and comprises water, a carbohydrate source, a nitrogen source and a number of free amino acids in an initial concentration wherein the initial concentration of each free amino acid is not limiting for the production of the toxin.

Abstract: The invention provides, inter alia, immunogenic compositions comprising a first antigen, at least two adjuvants, wherein a first adjuvant comprises a polymer derived from poly(lactides) and/or poly(lactide-co-glycolides), and wherein a second adjuvant comprises an imidazoquinoline, wherein said first antigen is encapsulated within, adsorbed or conjugated to, co-lyophilized or mixed with said first adjuvant, and a pharmaceutically acceptable excipient, wherein said composition elicits a cellular immune response when administered to a vertebrate subject. The invention also provides methods of producing immunogenic compositions, methods for producing a cytotoxic-T lymphocyte (CTL) response in a vertebrate subject, and methods of immunization.

Abstract: Certain embodiments disclosed herein relate to compositions, methods, devices, systems, and products regarding frozen particles. In certain embodiments, the frozen particles include materials at low temperatures. In certain embodiments, the frozen particles provide vehicles for delivery of particular agents. In certain embodiments, the frozen particles are administered to at least one biological tissue.

Abstract: Disclosed are vaccines and vaccine adjuvants useful in the treatment and/or prevention of infection and diseases associated with infectious pathogens, such as tetanus, as well as diseases associated with biological toxins. Also provided are methods of preparing an adjuvant and the vaccine containing the adjuvant. Methods are also provided for vaccinating/immunizing an animal against infection and diseases associated with infectious pathogens, such as tetanus, and other diseases associated with biological toxins. Adjuvant materials are presented that are prepared from an extracellular matrix material. The adjuvants are demonstrated to enhance the immunogenicity of an infectious pathogen antigen or biological toxin antigen of interest, as well as to enhance the survival of an immunized animal.

Abstract: The present invention provides a vaccine composition comprising an effective amount of antigen or a nucleic acid encoding antigen, encapsulated in polymeric particles, wherein said polymeric particles comprises nanoparticles, microparticles or combinations thereof, wherein surprisingly the nanoparticle induces cellular response and the microparticle induces humoral response. The invention further provides a method of inducing cellular and/or humoral immune response.

Abstract: The present invention is in the field of pneumococcal capsular saccharide conjugate vaccines. Specifically, a multivalent Streptococcus pneumoniae immunogenic composition is provided with various conjugated capsular saccharides from different S. pneumoniae serotypes conjugated to 2 or more different carrier proteins, where the composition comprises serotype 19F capsular saccharide conjugated to diphtheria toxoid (DT) or CRM197, optionally wherein 19F is the only saccharide in the composition conjugated to diphtheria toxoid (DT) or CRM197.

Abstract: The hsp70 gene from an Arthrobacter species has been isolated and sequenced. The encoded protein is believed to be highly immunogenic, especially in fish, and also has utility as a non-specific adjuvant, and as an adjuvanting carrier for heterologous antigens.

Abstract: Disclosed herein are methods of modulation of the viability of a cell. Further disclosed herein are methods of modulating an immune response. Further disclosed herein are methods of identifying agents capable of modulation of the viability of a cell or an immune response. Further disclosed herein are agents and compositions capable of modulation of the viability of a cell or an immune response.

Abstract: Methods and apparatus are provided for applying an fragment of a neurotoxin such as the active light chain (LC) of the botulinum toxin (BoNT), such as one of the serotype A, B, C, D, E, F or G botulinum toxins, via permeabilization of targeted cell membranes to enable translocation of the botulinum neurotoxin light chain (BoNT-LC) molecule across the targeted cell membrane to the cell cytosol where a therapeutic response is produced in a mammalian system. The methods and apparatus include use of catheter based delivery systems, non-invasive delivery systems, and transdermal delivery systems.

Abstract: The present invention relates to an immuno-therapeutic and prophylactic vaccine comprising monocytes or immature myeloid cells (IMCs) loaded with the ligand of natural killer T cell and an antigen for the prevention and treatment of infectious disease or cancer, more precisely, an immuno-therapeutic and prophylactic vaccine comprising monocytes or IMCs loaded with ?-galactosylceramide (?GalCer), a kind of glycolipid and a natural killer T cell ligand, and antigen. Monocytes or immature myeloid cells (IMCs) therein, which are easily obtainable, unlike dendritic cells, not only induce a significant level of cytotoxic T lymphocyte responses but also have a prophylactic and therapeutic effect on malignant tumor. Therefore, the immuno-therapeutic and prophylactic vaccine of the present invention can be effectively used as an immunotherapeutic agent.

Abstract: The present invention relates to methods and compositions of modified variants of diphtheria toxin (DT) that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome. One aspect of the present invention relates to a polypeptide toxophore from a modified DT, wherein the mutation is the substitution or deletion at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of native DT. Another aspect of the present invention relates to a fusion protein which comprises a modified DT and a non-DT fragment. Another aspect of the present invention relates to the use of modified DT for the treatment of cancer.

Abstract: Improved vaccine compositions and methods of use thereof are described that elicit production of antibodies in an individual to the individual's own endogenous cholesteryl ester transfer protein (CETP).

Abstract: The present application relates to compositions of modified diphtheria toxin and fusion proteins containing modified diphtheria toxin that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome, as well as methods of making the compositions. The present application also relates to a polypeptide toxophore from a modified diphtheria toxin, where the modification is at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of an unmodified native diphtheria toxin. Also described are fusion proteins which contain a modified diphtheria toxin and a non-diphtheria toxin fragment which contains a cell binding portion. The modified diphtheria toxins described can be used for the treatment of a malignant disease or a non-malignant disease.

Abstract: The present invention relates to adjuvant compositions which are suitable to be used in vaccines. In particular, the adjuvant compositions of the present invention comprises a saponin and an immunostimulatory oligonucleotide, optionally with a carrier. Also provided by the present invention are vaccines comprising the adjuvants of the present invention and an antigen. Further provided are methods of manufacture of the adjuvants and vaccines of the present invention and their use as medicaments. Methods of treating an individual susceptible to or suffering from a disease by the administration of the vaccines of the present invention are also provided.

Abstract: The present invention provides a composition for osteoinduction, which comprises a complexed-acidic-phospholipid complex containing calcium, phospholipid, and inorganic phosphate combined with collagen in a composite form. The composition is effective to promote new bone formation upon introduction of the composition into various osseous defects.

Abstract: Mucosal DTPa vaccines, especially intranasal vaccines, comprising (a) a diphtheria antigen, a tetanus antigen and an acellular pertussis antigen, and (b) a detoxified mutant of cholera toxin (CT) or E. coli heat labile toxin (LT). Component (b) acts as a mucosal adjuvant. The acellular pertussis antigen preferably comprises pertussis holotoxin (PT) and filamentous haemagglutinin (FHA) and, optionally, pertactin. The mucosally-delivered combined DTPa formulation is capable of generating a level of protection against B. pertussis infection equivalent to that observed by alum-adjuvanted parenteral administration.

Abstract: The present invention pertains generally to novel Neisseria meningitidis serogroup B glycoconjugates. More particularly, the invention pertains to glycoconjugates formed from a Neisseria meningitidis serogroup B capsular oligosaccharide derivative (MenB OS derivative) in which sialic acid residue N-acetyl groups are replaced with N-acyl groups. The invention also pertains to vaccine formulations containing the glycoconjugates, methods of making the vaccine formulations, and methods of using the vaccine formulations to treat or prevent Neisseria meningitidis serogroup B or E. coli K1 disease in a mammalian subject.

Abstract: Immunogenic polypeptides comprising hepatitis C virus (HCV) immunogens are described. The HCV immunogen comprises the amino acid sequence Xaa-Thr-Xaa-Val-Thr-Gly-Gly-Xaa-Ala-Ala-Arg-Thr-Thr-Xaa-Gly-Xaa-Xaa-Ser-Leu-P he-Xaa-Xaa-Gly-Xaa-Ser-Gln-Xaa-Ile-Gln-Leu-Ile (SEQ ID NO:8). The immunogenic polypeptide can be coupled to a bacterial toxoid, such as a diphtheria toxoid.

Abstract: A method of delivering a protein to domestic poultry by administering to the poultry by whole body spray an effective amount of a live avirulent derivative of an enteropathogenic bacterium that contains a recombinant gene encoding the protein.

Abstract: The invention provides fusion toxins that contain one or more regions of diphtheria toxin and a portion of urokinase-type plasminogen activator, as well as the nucleic acids that encode the fusion toxins and methods of using the fusion toxins.

Abstract: This invention pertains to vaccine compositions comprising a mixture of antigen, such as pneumococcal or meningococcal antigen, and interleukin IL-12, which may be adsorbed onto a mineral in suspension. The pneumococcal or meningococcal antigen may be conjugated to a carrier molecule. These vaccine compositions modulate the protective immune response to the antigen.

Abstract: The present invention relates to vaccine compositions comprising iron phosphate as adjuvant. This iron phosphate is in the form of particles, the size of which is between 0.01 &mgr;m and 300 &mgr;m; it can be obtained by mixing a solution of iron salt and of phosphate salt.

Abstract: The invention relates to certain stable vaccine compositions comprising a macrocyclic lactone compound, a milbemycin compound, an avermectin compound or mixtures thereof; at least one antigen; a dispersing agent; an adjuvant; a water soluble organic solvent; and saline or water or mixtures thereof. The invention further relates to stable compositions as described above of a macrocyclic lactone compound, a milbemycin compound, an avermectin compound or mixtures thereof, but without an antigen. The invention also relates to a method for preventing or controlling helminthiasis, infection by acarids and arthropod endo-and ectoparasites and bacterial and viral disease in warm-blooded animals by the parenteral administration of compositions of the invention. The invention further relates to a process for the preparation of the invention compositions.

Abstract: Apoptosis-modifying fusion polypeptides, and the corresponding nucleic acid molecules, are disclosed. Pharmaceutical compositions comprising these polypeptides, and the use of these polypeptides to modify apoptosis are also provided.

Abstract: The present invention relates to combination vaccines comprising a conjugated polysaccharide antigen linked to a carrier protein, and wherein the carrier protein is also present as a free antigen in the vaccine composition, characterised in that the ratio of polysaccharide to protein is from 1:0:3 to 1:2. In particular, the vaccine composition of the present invention relates to a multivalent vaccine, that is a vaccine for the amelioration or treatment of more than one disease state. The present invention also relates to the production and use of such a vaccine in medicine.

Abstract: The invention relates to the use of a composition comprising n Streptococcus pneumoniae polysaccharides conjugated to the tetanus toxoid and p Streptococcus pneumoniae polysaccharides conjugated to the diphtheria toxoid, for manufacturing a vaccine which protects against Clostridium tetani and/or Corynebacterium diphtheriae infections in which:

Abstract: An immunomodulator having suppressive activity on IgE antibody production is provided and contains bacterial cells, or their decomposition materials. It can be taken as a food. Bacterial cells such as Corynebacterium, Brevibacterium, Microbacterium, or bacterial cells of mutant strains of these bacteria, or decomposition products of these bacteria are used.