Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Abstract: A bacterial cell which expresses three or more coli surface (CS) antigens and methods of making such a cell. The cell is useful in making vaccines against diarrhea.

Abstract: The present invention relates to live attenuated bacteria for use in a medicament. The invention also relates to vaccines based upon such bacteria useful for the prevention of microbial pathogenesis and to the use of such bacteria for the manufacture of a vaccine. Finally, the invention relates to methods for the preparation of such vaccines.

Abstract: The invention provides strains of bacteria, especially enterotoxigenic E. coli, attenuated by mutations in the genes encoding enterotoxins (LT, ST, EAST1) and optionally further attenuated by deletion of additional chromosomal genes. In addition the invention provides strains of attenuated bacteria expressing immunogenic but non-toxic variants of one or more of these enterotoxins. These bacteria are useful as a vaccine against diarrhoeal disease.

Abstract: Safe and effective live vaccines against Aeromonas hydrophila of fish were created through the induction of rifampicin resistance in native Aeromonas hydrophila isolates; these including rifampicin-resistant mutants NRRL-B-50040 and NRRL-B-50041. Single immersion exposure of fish stimulated acquired immunity against virulent Aeromonas hydrophila infection.

Abstract: The present technology provides vaccine compositions comprising native outer membrane vesicles (NOMVs) from at least one genetically modified strain of Neisseria which provides protective immunity to meningococcal disease, more preferably subtype B meningococcal disease. The present technology further provides methods of immunizing an animal or human against meningococcal disease comprising administering the vaccine composition of the present invention.

Abstract: Francisella tularensis is the bacterial pathogen that causes tularemia in humans and a number of animals. To date, no approved vaccine exists for this widespread and life-threatening disease. The present disclosure provides attenuated Francisella mutants that include functional deletions in one or more of the dsbB, FTT0742, pdpB, fumA, and carB genes. Also provided are immunogenic compositions that include the attenuated bacteria. Methods are provided for treatment using the attenuated Francisella mutants.

Abstract: The present invention relates to an attenuated Salmonella typhi having mutation in chromosomal gene loci, its use as a potent vaccine candidate to combat the Salmonella infection.

Abstract: The invention relates to Pasteurella multocida mutants capable of providing heterologous protection against infection caused by virulent P. multocida. Said mutants are defective in fur ompH and fur ompH galE genes. The invention relates to Pasteurella multocida bacteria vaccine compositions containing fur ompH double mutants and fur ompH galE triple mutants obtained from P. multocida, or an extract of iron-regulated outer-membrane proteins (IROMPs) obtained from said mutants, and to an excipient and/or pharmaceutically acceptable adjuvants.

Abstract: Free-living microbes are provided in which the nucleic acid has been modified so that the microbe is attenuated for proliferation and/or which comprise genetic mutations that attenuate the ability of the microbe to repair its nucleic acid. Methods of using the modified microbes for the loading, activation, and/or maturation of antigen-presenting cells are also provided. Vaccine compositions comprising the modified microbes and/or the antigen-presenting cells and methods of using the vaccines are also provided. The microbes may be further modified to include heterologous antigens, such as tumor antigens or infectious disease antigens, for use as a vaccine against cancer or infectious diseases.

Abstract: An isolated strain of Enterococcus faecalis GALT deposited under number CECT 7121 of the group of lactic bacteria is disclosed, which is capable of surviving and colonizing the gastrointestinal tract of humans and/or animals and showing beneficial probiotic activity for the health of humans and animals. The strain E. faecalis GALT and/or a culture supernatant and/or metabolites thereof shows no in vitro multiresistance to antibiotics of common use in human clinics as glycopeptides, such as vancomycin, teicoplanine; carbapenemes, such as impipenem, meropenem; and ampicillin. The strain E. faecalis GALT contains no red blood cell-destroying hemolysins of human, ovine and equine origin; and it does not produce any gelatinase, DNase and decarboxylases. The strain E.

Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Abstract: The present invention discloses attenuated Clostridium perfringens organisms that express a substantially nontoxic alpha-toxin. The expressed alpha-toxin is a deletion mutein that relative to the alpha-toxin of the mature alpha-toxin of Clostridium perfringens strain 13, is missing at least nine consecutive amino acid residues including His68. The present invention also discloses attenuated organisms that encode the muteins, as well as the use of such attenuated organisms as vaccines.

Abstract: The ospF gene of Shigella flexneri encodes a phosphatase, which is a member of a new class of phosphatases. The OspF phosphatase inhibits the activity of several proteins either by direct protein modification or transcription downregulation. These proteins include MAP kinase, IL-8, CCL20, IL-12, AP1, CREB, RPA p32, and BCL2 related proteins. Methods for treating diseases using OspF phosphatase, methods for identifying agents that modulate OspF phosphatase's activity, methods for identifying agents that mimic OspF phosphatase's activity, and immunogenic compositions comprising OspF phosphatase are provided. A strain of Shigella flexneri containing an inactivated ospF gene is also provided.

Abstract: A series of genes from Salmonella typhimurium are shown to encode products which are implicated in virulence. The identification of these genes therefore allows attenuated microorganisms to be produced. Furthermore, the genes or their encoded products can be used in the manufacture of vaccines for therapeutic application.

Abstract: The present invention provides recombinant nucleic acid molecules, expression cassettes, and vectors useful for expression of polypeptides, including heterologous polypeptides, such as antigens, in bacteria. Some of the recombinant nucleic acid molecules, expression cassettes and vectors comprise codon-optimized sequences encoding the polypeptides and/or signal peptides. Some of the recombinant nucleic acid molecules, expression cassettes, and expression vectors comprise sequences encoding non-Listerial and/or non-secA1 signal peptides for secretion of the polypeptides. The invention also provides bacteria comprising the nucleic acid molecules, expression cassettes, and expression vectors, as well as compositions such as vaccines comprising the bacteria. Methods of making and using the bacteria, recombinant nucleic acid molecules, and expression cassettes are also provided.

Abstract: This invention is directed to applying a low sedimental fluid shear environment to manipulate microorganisms, and to microorganisms and compositions obtained based on such manipulation. Specifically, the present invention provides methods of modifying a molecular genetic or phenotypic characteristic (e.g., virulence, stress resistance or biofilm formation) of a microorganism by culturing in a low sedimental shear environment. One or more ion concentrations in the culture can be modulated in order to inhibit or amplify the extent of the modification. The present invention also provides microorganisms obtained from a low sedimental shear culture, which exhibit modified and desirable phenotypic characteristics, as well as therapeutic, vaccine and bioindustrial products prepared from such microorganisms.

Abstract: Free-living microbes are provided in which the nucleic acid has been modified so that the microbe is attenuated for proliferation and/or which comprise genetic mutations that attenuate the ability of the microbe to repair its nucleic acid. Methods of using the modified microbes for the loading, activation, and/or maturation of antigen-presenting cells are also provided. Vaccine compositions comprising the modified microbes and/or the antigen-presenting cells and methods of using the vaccines are also provided. The microbes may be further modified to include heterologous antigens, such as tumor antigens or infectious disease antigens, for use as a vaccine against cancer or infectious diseases.

Abstract: Live attenuated Eastern Equine Encephalitis (EEE) vaccines that outperform the PE-6 vaccine in mice aerosol challenged with >1,000×LD50. Candidates include four furin-cleavage deletion mutants and one E3 deletion mutant. Each vaccine provided protection in birds against antigenically distinct North and South American strains of EEE. The PE-6 vaccine does not provide protection against South American EEEs. Animals inoculated with each of the vaccines of the invention developed neutralizing antibodies to EEE.

Abstract: The present invention relates to a combination vaccine for the protection of poultry against Ornithobacterium rhinotracheale, to the use of a live over-attenuated Ornithobacterium rhinotracheale strain and a live attenuated poultry virus for the manufacturing of such a combination vaccine, to methods for the preparation of said combination vaccine and to vaccination kits for the immunization of poultry against Ornithobacterium rhinotracheale.

Abstract: The present invention discloses attenuated Clostridium perfringens organisms that express a substantially nontoxic alpha-toxin. The expressed alpha-toxin is a deletion mutein that relative to the alpha-toxin of the mature alpha-toxin of Clostridium perfringens strain 13, is missing at least nine consecutive amino acid residues including His68. The present invention also discloses attenuated organisms that encode the muteins, as well as the use of such attenuated organisms as vaccines.

Abstract: The invention provides Listeria that, in addition to comprising polynucleotides that encode heterologous polypeptides such as tumor or infectious agent antigens, have been modified to express holin proteins that facilitate the delivery of the heterologous polypeptides, or polynucleotides encoding the same, outside of the bacteria. In some particular embodiments, the Listeria generate viral-derived, self-replicating RNAs that direct expression of the heterologous polypeptides in the cytosol of infected cells. Methods of using the Listeria, and compositions thereof, to induce immune response and/or in the prevention or treatment of disease are also provided. Methods of producing the bacteria are also provided.

Abstract: Free-living microbes are provided in which the nucleic acid has been modified so that the microbe is attenuated for proliferation and/or which comprise genetic mutations that attenuate the ability of the microbe to repair its nucleic acid. Methods of using the modified microbes for the loading, activation, and/or maturation of antigen-presenting cells are also provided. Vaccine compositions comprising the modified microbes and/or the antigen-presenting cells and methods of using the vaccines are also provided. The microbes may be further modified to include heterologous antigens, such as tumor antigens or infectious disease antigens, for use as a vaccine against cancer or infectious diseases.

Abstract: The present invention provides Listeria that are attenuated for entry into non-phagocytic cells as well as a variety of methods of inducing immune responses involving administering compositions comprising the attenuated Listeria. Some of the attenuated Listeria are mutant Listeria that comprise at least one mutation in a gene encoding an invasin, such as an internalin. Some of the attenuated Listeria are further attenuated for cell-to-cell spread. Pharmaceutical compositions and vaccines useful in the methods of the invention are further provided. Methods of making and improving vaccines are also provided.

Abstract: Free-living microbes are provided in which the nucleic acid has been modified so that the microbe is attenuated for proliferation and/or which comprise genetic mutations that attenuate the ability of the microbe to repair its nucleic acid. Methods of using the modified microbes for the loading, activation, and/or maturation of antigen-presenting cells are also provided. Vaccine compositions comprising the modified microbes and/or the antigen-presenting cells and methods of using the vaccines are also provided. The microbes may be further modified to include heterologous antigens, such as tumor antigens or infectious disease antigens, for use as a vaccine against cancer or infectious diseases.

Abstract: Antigenic compositions are provided comprising a single chain polypeptide comprising first and second domains, wherein said first domain is a clostridial neurotoxin light chain or a fragment or a variant thereof and is capable of cleaving one or more vesicle or plasma membrane associated proteins essential to exocytosis; and said second domain is a clostridial neurotoxin heavy chain HN portion or a fragment or a variant thereof, wherein said second domain is capable of (i) translocating the polypeptide into a cell or (ii) increasing the solubility of the polypeptide compared to the solubility of the first domain on its own or (iii) both translocating the polypeptide into a cell and increasing the solubility of the polypeptide compared to the solubility of the first domain on its own; and wherein the second domain lacks a functional C-terminal part of a clostridial neurotoxin heavy chain designated HC thereby rendering the polypeptide incapable of binding to cell surface receptors that are the natural cell sur

Abstract: A chemical conjugate for treating a nerve cell related disorder is provided. This conjugate includes an active or inactive Clostridial toxin having specificity for a target nerve cell. The toxin is conjugated to a drug or other bioactive molecule without affecting the toxin's ability to enter the target nerve cell.

Abstract: The present invention relates to vaccines for control of Borrelia infections in animal and human populations. In particular, the present invention provides compositions and methods comprising recombinant bacteria engineered to express one or more Borrelia burgdorferi antigens for use as Lyme disease vaccines. In some embodiments, the recombinant bacteria are freeze-dried.

Abstract: Vaccines that comprise or generate immunomodulatory flagellin polypeptides able to stimulate an innate immune response intracellularly and extracellularly employ viruses, bacteria or parasitic cells that contain expression systems for such polypeptides, as well as fusion proteins that contain antigens and/or cell penetrating peptides along with the immunomodulatory peptide.

Abstract: The present invention relates to a method for producing carrier microorganisms, in particular bacteria, which, through targeted genetic manipulation, carry epitopes or epitomers, respectively, on their surfaces. Epitomers are antigenically effective epitopes that can be found in the polypeptide chain in multiple identical copies, and which, when expressed on the surface of the bacteria, can be used for immunization with particular success. A further aspect relates to correspondingly produced bacteria and their uses as vaccines, in particular in cancer therapy.

Abstract: Disclosed are compositions, kits, and methods for activating, expanding, or stimulating ?? T cells that include recombinant attenuated microbes. The compositions may include pharmaceutical compositions that are used as ?? T cell stimulating vaccines or immunogenic compositions for preventing or treating microbial infections and hyperplasias such as cancer.

Abstract: A biologically pure RNAIII inhibiting peptide (RIP), that includes five contiguous amino acids of the sequence YX2PX1TNF, where X1 is C, W, I or a modified amino acid, and X2 is K or S is provided. The RIP further includes amino acids having a sequence that differs from the sequence YX2PX1TNF by two substitutions or deletions, where X1 is C, W, I or a modified amino acid, and X2 is K or S. This agent offers improved protection against and treatment of staphylococcal infections, and related bacteria infections, in mammals.

Abstract: A vaccine delivered by transcutaneous immunization provides an effective treatment against infections by pathogens such as, for example, enterotoxigenic Escherichia coli (ETEC) and/or for symptoms of diarrheal disease caused thereby. For example, one, two, three, four, five or more antigens derived from ETEC and capable of inducing an antigen-specific immune response (e.g., toxins, colonization or virulence factors) and one or more optional adjuvant (e.g., whole bacterial ADP-ribosylating exotoxins, B subunits or toxoids thereof, detoxified mutants and derivatives thereof) are used to manufacture vaccines or to induce systemic and/or mucosal immunity.

Abstract: The present invention is directed to mutant Salmonella sp. having a genetically modified msbB gene in which the mutant Salmonella is capable of targeting solid tumors. The present invention further relates to the therapeutic use of the mutant Salmonella for growth inhibition and/or reduction in volume of solid tumors.

Abstract: The invention concerns an acellular immunogenic or vaccine composition for producing antibodies against Bacillus anthracis comprising a protective antigen (PA) and killed and optionally purified spores, obtained from mutating strains of Bacillus anthracis and their uses.

Abstract: The invention relates to a viral vaccine, especially a retroviral vaccine, and methods of forming such a vaccine. The vaccine is formed from a whole-killed virus suspension in a cell lysate or culture medium, wherein the virus is killed by exposure to a chloramine compound at a level adequate to inactivate zinc finger proteins. The chloramine compound may be taurine chloramine, adenosine chloramine, phenylalanine chloramine, and alanine chloramine. The vaccine may be used as a prophylactic or therapeutic vaccine and may be developed from a subject's own strains of virus so as to be considered an autologous vaccine.

Abstract: The present invention is directed to a pharmaceutical preparation for oral application for treatment of fish, in particular for vaccination of fish of the salmon family and other fish having a comparable digestive system against bacterial and/or viral infections, in particular against VHS and IHN. The invention is also directed to a method for producing the preparation.

Abstract: The present invention generally provides methods and compositions for eliciting an immune response against Neisseria spp. bacteria in a subject, particularly against a Neisseria meningitidis serogroup B strain.

Abstract: Compositions comprising activatable recombinant neurotoxins and polypeptides derived therefrom. The invention also comprises nucleic acids encoding such polypeptides, and methods of making such polypeptides and nucleic acids.

Abstract: A method for identifying a microorganism having a reduced adaptation to a particular environment comprising the steps of: (1) providing a plurality of microorganisms each of which is independently mutated by the insertional inactivation of a gene with a nucleic acid comprising a unique marker sequence so that each mutant contains a different marker sequence, or clones of the said microorganism; (2) providing individually a stored sample of each mutant produced by step (1) and providing individually stored nucleic acid comprising the unique marker sequence from each individual mutant; (3) introducing a plurality of mutants produced by step (1) into the said particular environment and allowing those microorganisms which are able to do so to grow in the said environment; (4) retrieving microorganisms from the said environment or a selected part thereof and isolating the nucleic acid from the retrieved microorganisms; (5) comparing any marker sequences in the nucleic acid isolated in step (4) to the unique mar

Abstract: The present invention relates to live attenuated Salmonella cultures for use as vaccines. The Salmonella cultures of the present invention have a substantially reduced capacity to grow and replicate in the presence of bile. The reduced capacity for growth is due to a metabolic-drift mutation induced by exposure to a combination of nalidixic acid and rifampicin for a time and under conditions sufficient to induce the mutation.

Abstract: The present invention discloses a synergistic effect between vaccines encoding tumor-associated antigen and vaccines encoding tumor endothelial marker (8) (TEM8). Potent antitumor immunity was generated by the combined use of these vaccines. Tumor supported by vasculature and for which a tumor-associated antigen has been defined can be treated with this approach.

Abstract: A method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of Botulinum toxin types A, B, C, D, E, F and G.

Abstract: The present invention is directed to mutant Salmonella sp. having a genetically modified msbB gene in which the mutant Salmonella is capable of targeting solid tumors. The invention is also directed to Salmonella sp. containing a genetically modified msbB gene as well as an genetic modification in a biosynthetic pathway gene such as the purl gene. The present invention further relates to the therapeutic use of the mutant Salmonella for growth inhibition and/or reduction in volume of solid tumors.

Abstract: Acapsular hyaE deletion mutants of P. multocida can be administered to mammals, particularly ungulates, or birds to provide protective immunity against wild-type P. multocida, e.g., to prevent or reduce the severity of hemorrhagic septicemia or pneumonia in mammals, particularly livestock, ungulates, and companion animals, or fowl cholera in birds, particularly poultry.

Abstract: The present invention is directed to compounds and methods for immunizing a patient against a biofilm-producing bacterial infection and a vaccine related thereto.

Abstract: Mutant strains of Rhodococcus equi are disclosed, and vaccines comprising same.

Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.

Abstract: The invention relates to peptides having an amino acid sequence substantially homologous to an amino sequence of a domain of a pyrogenic exotoxin, which domain forms a central turn in the exotoxin starting within ?-strand 7 and connecting the ?-strand 7, via short ?-strand 8, to ?-helix 4, and ending within ?-helix 4, based on the domain numbering of Staphylococus aureus enterotoxin B. The peptides of the invention are capable of antagonizing toxin-mediated activation of T-lymphocytes, do not have agonist activity, and are capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins.