Abstract: The invention relates to Salmonella typhi Ty21a comprising core-linked Shigella dysenteriae type 1 O-specific polysaccharide (O-Ps) and DNA encoding O antigen biosynthesis, said DNA selected from the group consisting of: a) the DNA sequence set out in any one of SEQ ID NOs: 1 and 2 and species homologs thereof; b) DNA encoding S. dysenteriae polypeptides encoded by any one of SEQ ID NOs: 1 and 2, and species homologs thereof; and c) DNA encoding a O antigen biosynthesis gene product that hybridizes under moderately stringent conditions to the DNA of (a) or (b); and related sequences, compositions of matter, vaccines, methods of using, and methods of making.

Abstract: A vaccine composition comprising two valences is provided: (i) a first valence which is adjuvant-enhanced with aluminum hydroxide and (ii) a second valence which contains a polysaccharide of bacterial capsule comprising one or more o-acetyl groups and which is not adsorbed with aluminum oxide due to the presence of a protecting compound which may be a phosphate, a citrate or a carbonate and which prevents the adsorption. The first valence can be any vaccine valence. In one particular embodiment, the vaccine composition contains (i) Hepatitis A valence, adsorbed on aluminum hydroxide and (ii) the typhoid fever valence formed by the polysaccharide Vi of the Salmonella typhi capsule.

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 provides methods for reducing shedding in an animal. Generally, the method includes administcriirn to an animal a composition including siderophore receptor polypeptides and porins from gram negative microbes, and preferably, lipopolysaccarhide at a concentration of no greater than about 10.0 endotoxin units per milliliter.

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: The present invention provides methods for treating mastitis in a milk producing animal. The methods include administering compositions including siderophore receptor polypeptides and porins from gram negative microbes, and preferably, lipopolysaccarhide at a concentration of no greater than about 10.0 endotoxin units per milliliter.

Abstract: There is provided a vaccine composition comprising a combination of a genetic deletion mutant S. typhimurium microorganism and a genetic deletion mutant E. coli microorganism, suitable for mass application to poultry. Also provided is a safe and effective method to protect poultry against the ravages of E. coli and Salmonella infection and disease.

Abstract: Methods and compositions for detecting and localizing light originating from a mammal are disclosed. Also disclosed are methods for targeting light emission to selected regions, as well as for tracking entities within the mammal. In addition, animal models for disease states are disclosed, as are methods for localizing and tracking the progression of disease or a pathogen within the animal, and for screening putative therapeutic compounds effective to inhibit the disease or pathogen.

Abstract: The present invention pertains to a Salmonella microorganism having an attenuating mutation which disrupts the expression of a gene located within the Spi2 pathogenicity island, and an auxotrophic mutation. The microorganism therefore has a double mutation which helps prevent reactivity of the microorganism while maintaining the effectiveness of the microorganism to elicit an immune response. The present invention also pertains to vaccine compositions and methods for treating and preventing a Salmonella infection in a patient.

Abstract: Methods and compositions for detecting and localizing light originating from a mammal are disclosed. Also disclosed are methods for targeting light emission to selected regions, as well as for tracking entities within the mammal. In addition, animal models for disease states are disclosed, as are methods for localizing and tracking the progression of disease or a pathogen within the animal, and for screening putative therapeutic compounds effective to inhibit the disease or pathogen.

Abstract: The present invention provides methods for making compositions including siderophore receptor polypeptides and porins from gram negative microbes. The methods include providing a gram negative microbe, disrupting the microbe, solubilizing the disrupted microbe, and isolating the polypeptides.

Abstract: The present invention provides methods for treating an animal having a high somatic cell count. The methods include administering compositions including siderophore receptor polypeptides and porins from gram negative microbes, and preferably, lipopolysaccarhide at a concentration of no greater than about 10.0 endotoxin units per milliliter.

Abstract: The present invention provides compositions including at least two siderophore receptor polypeptides and at least two porins from a gram negative microbe, and preferably, lipopolysaccharide at a concentration of no greater than about 10.0 endotoxin units per milliliter. The present invention also provides methods of makino and methods of using such compositions.

Abstract: The present invention provides methods for treating an animal for low milk production. The methods include administering compositions including siderophore receptor polypeptides and porins from gram negative microbes, and preferably, lipopolysaccarhide at a concentration of no greater than about 10.0 endotoxin units per milliliter.

Abstract: Biodegradable and biocompatible polymeric microspheres encapsulating Salmonella enteritidis are administered to chickens to provide the chickens with sustained protection against S. enteritidis infections.

Abstract: The present invention is directed to an attenuated Salmonella comprising a eukaryotic expression vector for delivery of the eukaryotic expression vector to a eukaryotic cell. Delivery may be to eukaryotic cells cultured in vitro or to cells in vivo, such as by oral administration of the attenuated Salmonella comprising the eukaryotic expression vector.

Abstract: Mycobacterium tuberculosis protein having a molecular weight of 28 779 Da, and hybrid proteins containing at least portions of its sequence. These proteins may in particular be used in vaccines or for the detection of specific tuberculosis antibodies.

Abstract: Attenuated immunogenic bacteria having an RpoS+ phenotype, in particular, Salmonella enterica serotype Typhi having an RpoS+ phenotype and methods therefor are disclosed. The Salmonella have in addition to an RpoS+ phenotype, an inactivating mutation in one or more genes which render the microbe attenuated, and a recombinant gene capable of expressing a desired protein. The Salmonella are attenuated and have high immunogenicity so that they can be used in vaccines and as delivery vehicles for genes and gene products. Also disclosed are methods for preparing the vaccine delivery vehicles.

Abstract: The present invention relates to live attenuated Salmonella strains comprising a first attenuating mutation, that are not capable of making functional RecA. The invention also relates to these bacteria for use in vaccines. Furthermore, the invention relates to vaccines based upon these bacteria, to the use of such bacteria in the manufacture of vaccines and to methods for the preparation of such vaccines.

Abstract: The present invention provides vaccine compositions comprising an oil-in-water emulsion optionally with 3 De-O-acylated monophosphoryl lipid A and QS21. The vaccine compositions are potent induces of a range of immune responses.

Abstract: The present invention relates generally to a Plasmid Maintenance System for the stabilization of expression plasmids encoding foreign antigens, and methods for making and using the Plasmid Maintenance System. The invention optimizes the maintenance of expression plasmids at two dependent levels by: (1) removing sole dependence on balanced lethal maintenance functions; and (2) incorporating at least one plasmid partition function to present random segregation of expression plasmids, thereby enhancing their inheritance and stability. The Plasmid Maintenance System may be employed within a plasmid which has been recombinantly engineered to express a variety of expression products.

Abstract: A vaccine is disclosed which is useful for protecting a host from Gram negative infections and the effects of endotoxin, therefore preventing sepsis and septic shock. The vaccine is prepared by combining LPS free or in conjugate form with a stoichiometric excess of a peptide of the formula: (a) (A)n wherein A is Lysine or Arginine and n is an integer with a minimum value of 7; (b) (AB)m wherein A is Lysine or Arginine and B is a hydrophobic amino acid selected from the group consisting of Valine, Leucine, Isoleucine, Tyrosine, Phenylalanine and Tryptophan; m is an integer with a minimum value of 3; and (c) (ABC)p wherein A is a cationic amino acid which is Lysine or Arginine; B and C are hydrophobic amino acids which may be the same or different and are selected from the group consisting of Valine, Leucine, Isoleucine, Tyrosine, Phenylalanine and Tryptophan; p is an integer with a minimum value of 2.

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 relates to a vaccine comprising a bacterium attenuated by a non-reverting mutation in a gene encoding a protein which promotes folding of extracytoplasmic proteins. Such mutations were initially identified as being useful in vaccines from a bank of randomly inserted, transposon mutants in which attenuation was determined as a reduction in virulence of the organism in the mouse model of infection. Site directed mutation of the gene results in a strain which shows at least 4 logs of attenuation when delivered both orally and intravenously. Animals vaccinated with such a strain are protected against subsequent challenge with the parent wild type strain. Finally, heterologous antigens such as the non-toxic and protective, binding domain from tetanus toxin, fragment C, can be delivered via the mucosal immune system using such strains of bacteria. This results in the induction of a fully protective immune response to subsequent challenge with native tetanus toxin.

Abstract: The invention encompasses methods of maintaining desired recombinant genes in a genetic population of cells expressing the desired gene. The methods utilize microbial cells that have an inactivating mutation in a native essential gene encoding an enzyme which catalyzes a step in the biosynthesis of diaminopimelic acid (DAP). The cells also have an extrachromosomal vector that includes the desired gene and which is capable of homologous recombination with a chromosome of the microorganism. The vector also has a recombinant complementing gene encoding a functional replacement of the native essential gene. The cells of the invention are particularly useful for components of vaccines, including DNA vaccines.

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 purI 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: Substantially pure Salmonella secreted proteins (Ssp), the sercetion of which is dependent upon the expession of PrgH; methods of diagnosing Salmonella infection; and live attenuated vaccine strains in which Ssp secretion is decreased.

Abstract: This invention relates to conjugates of the O-specific polysaccharide of E. coli O157 with a carrier, and compositions thereof, and to methods of using of these conjugates and/or compositions thereof for eliciting an immunogenic response in mammals, including responses which provide protection against, or reduce the severity of, bacterial infections. More particularly it relates to the use of polysaccharides containing the tetrasaccharide repeat unit: (?3)-?-D-GalpNAc-(1?2)-?-D-PerpNAc-(1?3)-?-L-Fucp-(1?4)-?-D-Glcp-(1?), and conjugates thereof, to induce serum antibodies having bactericidal (killing) activity against hemolytic-uremic syndrome (HUS) causing E. coli, in particular E. coli O157. The conjugates, and compositions thereof, are useful as vaccines to induce serum antibodies which have bactericidal or bacteriostatic activity against against E. coli, in particular E. coli O157, and are useful to prevent and/or treat illnesses caused by E. coli O157.

Abstract: The present invention provides methods of inducing immune responses by recombinant antigen-enterotoxin chimeric mucosal immunogens that contain the A2/B subunits of cholera toxin or heat-labile type II toxins. These chimeric immunogens differentially enhance antibody secretion, cytokine production, as well as B7-dependent co-stimulation of T cells and CD40L expression on CD4+ T cells.

Abstract: The production of a purified extracellular bacterial signal called autoinducer-2 is regulated by changes in environmental conditions associated with a shift from a free-living existence to a colonizing or pathogenic existence in a host organism. Autoinducer-2 stimulates LuxQ luminescence genes, and is believed also to stimulate a variety of pathogenesis related genes in the bacterial species that produce it. A new class of bacterial genes is involved in the biosynthesis of autoinducer-2.

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 againt S. typhi and are useful to prevent and/or treat illnesses caused by S. typhi.

Abstract: The present invention relates to a process for the preparation of a vaccine against tuberculosis and other intracellular pathogens, this vaccine is targeted against intracellular pathogens, more particularly the pathogen Mycobacterium tuberculosis and Salmonella in this case.

Abstract: The present invention relates to live attenuated bacteria for use as a medicament. The invention also relates to vaccines based thereon that are useful for the prevention of microbial pathogenesis. Further, the invention relates to live attenuated recombinant bacteria carrying a heterologous gene and vaccines based thereon. Finally, the invention relates to methods for the preparation of such vaccines and bacteria.

Abstract: The present invention pertains to a Salmonella microorganism having an attenuating mutation which disrupts the expression of a gene located within the Spi2 pathogenicity island, and an auxotrophic mutation. The microorganism therefore has a double mutation which helps prevent reactivity of the microorganism while maintaining the effectiveness of the microorganism to elicit an immune response. The present invention also pertains to vaccine compositions and methods for treating and preventing a Salmonella infection in a patient.

Abstract: Compare core LPS (lacking O-polysaccharide side chains) from Gram-negative bacteria are incorporated into a vaccine typically in liposomes. The complete core of E. coli K 12 is particularly useful. Upon administration to a mammal the vaccine stimulates synthesis of antibodies which are cross-protective against smooth and rough forms of LPS from at least two different Gram-negative bacterial strains having different core structures.

Abstract: Compositions and methods for making complex carbohydrates in a bacterial production cell are disclosed. The complex carbohydrates that can be made include oligosaccharides and polysaccharides of bacterial or mammalian origin.

Abstract: A method of vaccinating poultry by spraying the poultry with an effective amount of a live avirulent derivative of an enteropathogenic enterobacteria is disclosed.

Abstract: The invention provides a DNA molecule comprising a promoter sequence operably linked to a DNA sequence encoding first and second proteins linked by a hinge region wherein in that the promoter sequence can be one having activity which is induced in response to a change in the surrounding environment and the first protein can be Tetanus toxin C fragment or one or more epitopes thereof. The invention also provides intermediate molecules having a promoter operably linked to a DNA sequence encoding a first antigenic sequence and a hinge region, and at or adjacent the 3′-end thereof one or more restriction sites for the introduction of a second anti-genic sequence. In addition, the invention provides replicable expression vectors containing the DNA fusion proteins expressed therefrom, bacterial transformed with the vectors and the use of the bacteria, in vaccines.

Abstract: Attenuated mutant Salmonella bacteria containing inactivated virulence genes are provided for use in safe, efficacious vaccines.

Abstract: Mycobacterium tuberculosis protein having a molecular weight of 28.779 Da, and hybrid proteins containing at least portions of its sequence. These proteins may in particular be used in vaccines or for the detection of specific tuberculosis antibodies.

Abstract: The present invention provides attenuated live cultures of the pathogenic protozoan parasite, Neospora, and live vaccines against neosporosis prepared therefrom which are useful in the prevention of clinical disease and abortion in mammals.

Abstract: The present invention relates to a method of protecting pigs against disease caused by infection by heterologous serotypes of Salmonella including but not limited to S. typhimurium comprising administering to the pigs a modified live vaccine incorporating S. cholerasuis.

Abstract: Mucosal, particularly oral, microparticle conjugate vaccines against certain pathogenic microorganisms, especially intracellular pathogenic microorganisms, are disclosed. An immunizing component of such a vaccine comprises protection-generating antigens derived from a certain pathogenic microorganism, such as Mycobacterium tuberculosis or Salmonella enteritidis, conjugated, possibly via a linker, to biodegradable microparticles, particularly starch microparticles, such as cross-linked starch microparticles, e.g. polyacryl starch microparticles. Further, a method of inducing protective immunity against a certain pathogenic microorganism in a mammal, and the use of protection-generating antigens derived from a certain pathogenic microorganism conjugated, possibly via a linker to biodegradable microparticles for the production of a mucosal microparticle conjugate vaccine are described.

Abstract: An attenuated strain of Salmonella typhimurium has been used as a vehicle for oral genetic immunization. Eukaryotic expression vectors containing the genes for b-galactosidase, or truncated forms of ActA and listeriolysin—two virulence factors of Listeria monocytogenes—that were controlled by an eukaryotic promoter have been used to transform a S. typhimurium aroA strain. Multiple or even single immunizations with these transformants induced a strong cytotoxic and helper T cell response as well as an excellent antibody response. Multiple immunizations with listeriolysin transformants protected the mice completely against a lethal challenge of L. monocytogenes. Partial protection was already observed with a single dose. ActA appeared not to be a protective antigen.

Abstract: The present invention provides vaccine compositions comprising an oil-in-water emulsion optionally with 3 De-O-acylated monophosphoryl lipid A and QS21. The vaccine compositions are potent inducers of a range of immune responses.

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 present invention relates to live attenuated gram-negative vaccine carrier strains which are useful for expression and delivery of heterologous O-antigens (O-PS) from gram-negative pathogens. Said strains are deficient in the expression of homologous O-PS due to a defined genetic modification, preferably a deletion, and, thus, capable of efficiently expressing a desired heterologous O-PS in such a way that it is covalently coupled either to homologous or heterologous LPS core lipid A. The present invention furthermore relates to live vaccine carrier strains containing a heterologous gene or a set of heterologous genes encoding O-PS. Preferably, said strains additionally contain genes necessary for the synthesis of complete smooth heterologous LPS. The present invention also relates to live vaccines comprising said strains, preferably for immunization against gram-negative enteric pathogens.

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: This invention relates to a process for the preparation of Salmonella vaccine by treating entrotoxin and cytotoxins with formalin and adding immuno-potentiator selected from Freund's complete adjuvant (FCA) or Vitamin E or Saponin to said concentrated toxoids to get the desired vaccine. The present invention also provides a Salmonella vaccine for protection against Salmonellosis in poultry.

Abstract: Biologically active polypeptides and/or antigens are delivered by administering to a subject a non-invasive or non-pathogenic bacterium which expresses one or more antigens or polypeptides. The non-invasive or non-pathogenic bacterium can be included in delivery systems or pharmaceutical formulations.