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: It has been discovered that a vaccine comprised of fimbrin, a filamentous protein derived from the bacterial surface appendages of non-typable Haemophilus influenzae is useful in studying, preventing or reducing the severity of, otitis media. The gene sequence of the DNA coding for fimbrin and the amino acid sequence of fimbrin have also been determined. Vectors containing DNA coding for fimbrin have also been developed, and transformants have been prepared which contain such vectors and which express such DNA and provide a source of pure fimbrin.

Abstract: The present invention provides gram-negative bacterial strains that produce substantially pure non-pyrogenic lipopolysaccharide or lipid A. The present invention also relates to a use of said strains for the preparation of non-pyrogenic DNA and use of the same for introducing endogenous or foreign genes into animal cells or animal tissue. Further, the present invention relates to a use of said strains for the preparation of non-pyrogenic recombinant mammalian, protozoan and viral proteins. Furthermore, the present invention relates to a use of said strains for the preparation of non-pyrogenic bacterial vaccines and vaccine vectors. Yet a further use of the present invention relates to a use of said strains for the preparation of non-pyrogenic bacterial proteins and polysaccharides antigens for use as vaccines.

Abstract: Disclosed herein methods for producing live attenuated Salmonella typhi, Salmonella paratyphi A and B and other Salmonella mutants which can be used in vaccines to prevent diseases caused by Salmonella infection. These mutants can also be used to prevent or treat diseases caused by other bacterial strains, by viral and parasitic pathogens and by tumor cells.

Abstract: Disclosed are bacteria having virulence attenuated by a mutation to the regulatory gene poxR. Also disclosed is a method of producing bacteria having virulence attenuated by mutating to the regulatory gene poxR. Such bacteria are useful for inducing an immune response in an animal or human against virulent forms of the bacteria with reduced risk of a virulent infection. Such bacteria are also useful to allow use of normally virulent bacteria as research tools with reduced risk of virulent infection. In a preferred embodiment, poxR attenuated bacteria can be used as a vaccine to induce immunoprotection in an animal against virulent forms of the bacteria. The disclosed bacteria can also be used as hosts for the expression of heterologous genes and proteins or to deliver DNA for genetic immunization. Attenuated bacteria with such expression can be used, for example, to deliver and present heterologous antigens to the immune system of an animal.

Abstract: The present invention provides 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. The present invention also provides methods of making and methods of using such compositions.

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: A truncated SE fimbria antigen useful as an antigen for immunoassay diagnosis of Salmonella enteritidis (SE) infection or evidence of infection.

Abstract: A salmonella live vaccine produced from at least one attenuated immunologic live vaccine strain, characterized in that the vaccine strain has an envelope marker which results in an increased sensitivity of the vaccine strain toward a specific therapeutically effective antibiotic and has at least one chromosomal antibiotic resistance mutation for the attenuation.

Abstract: The 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 further relates to the therapeutic use of the mutant Salmonella for growth inhibition and/or reduction in volume of solid tumors.

Abstract: Attenuated strain of a prokaryotic microorganism, being an attenuated strain of Salmonella suitable for use in a live vaccine for administration to a human or animal, in which the microorganism is transformed with nucleic acid encoding Human papilloma virus 16 L1 major capsid protein. The protein assembles in the microorganism to form virus-like particles (VLPs) that are capable of illiciting an immune response sufficient to produce neutralizing antibodies in serum and genital secretions specific for Human papilloma 16 infection when the microorganism is administered to the human or animal body.

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: A method is provided for the formation of liposomes of 0.1 &mgr;m to 50 &mgr;m in diameter having unilamella or multilamella structure and containing water insoluble or undissolved particulate materials comprising (a) forming liposomes and removing substantially all of any organic solvent used in their preparation, (b) freeze drying the liposomes so formed and then (c) rehydrating them in intimate admixture with the particulate material. Preferred encapsulated materials are particulate materials, most preferably microorganisms, plant or animal cells or water insoluble structures having organic solvent labile biochemical or immunological activity, but any water insoluble particulate may be encapsulated using the method. For example catalysts or drugs that are sparingly soluble may also be so incorporated such that slow release into the a patients body may be provided while release of detergents included in the many liposome preparation protocols may be avoided.

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: The present invention is directed towards compositions containing pathogenic bacteria (e.g. Haemophilus, E. Coli, and/or Salmonella) having non-reverting genetic mutations which alter activity of DNA adenine methylase (Dam) and methods using these compositions to elicit an immune response to produce highly specific antibodies. The invention also provides methods for preparing vaccines as well as screening methods to identify agents which may have anti-bacterial activity.

Abstract: This invention relates to hepatitis B virus (“HBV”) core antigen particles that are characterized by multiple immunogen specificities. More particularly, the invention relates to HBV core antigen particles comprising immunogens, epitopes, or other related structures, crosslinked thereto by ligands which are HBV capsid-binding peptides that selectively bind to HBV core protein. Such particles may be used as delivery systems for a diverse range of immunogenic epitopes, including the HBV capsid-binding peptides, which advantageously also inhibit and interfere with HBV viral assembly by blocking the interaction between HBV core protein and HBV surface proteins. Mixtures of different immunogens and/or capsid-binding peptide ligands may be crosslinked to the same HBV core particle. Such resulting multicomponent or multivalent HBV core particles may be advantageously used in therapeutic and prophylactic vaccines and compositions, as well as in diagnostic compositions and methods using them.

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: A method for improving the immune response of an animal to a vaccine, comprising: feeding an animal a diet of contamination-resistant feed, and treating said animal with an anti-viral or anti-bacterial vaccine.

Abstract: A method for vaccinating poultry to prevent salmonellosis and other microbial-related health problems in humans is described. The method involves isolation of a poultry heterophil-adapted strain of a microorganism that may be used in a vaccine. A vaccine comprising a preparation of the poultry heterophil-adapted strain is administered to poultry to reduce the transmission of microorganisms causing salmonellosis and other illnesses.

Abstract: The present inventors have found that certain preparations containing LPS and/or lipid A variants, derivatives, and/or analogs demonstrate non-pyrogenic properties and exhibit anti-viral activities. In particular, non-pyrogenic preparations of LPS, lipid A, LPS antagonists and lipid A antagonists, and derivatives thereof induce &bgr; chemokine secretion, such as MIP-1&bgr;, but not proinflammatory cytokines, such as TNF&agr;, IL-1&bgr; and IL-6. Non-pyrogenic preparations of the invention have been demonstrated by the Applicant to suppress HIV replication in human peripheral blood monocytes, as described by way of example herein. The present invention provides preparations of LPS or lipid A variants, analogs and derivatives of decreased or absent pyrogenicity which can be used as therapeutics for the treatment or prevention of immunodeficiency virus infection and its consequences.

Abstract: This application relates to the use of attenuated prokaryotic microorganism strains (such as Salmonella ) expressing nucleic acid encoding HPV proteins as vaccines against HPV infection and the associated increased risk of cancer. In particular, the work shows that it is possible to assemble VLPs in a prokaryotic organism and that nasal immunization of mice with the strains HPV-specific conformationally dependent and neutralizing antibodies in serum and genital secretions. The experiments described herein show that it is also possible to assemble chimeric VLPs of an HPV including a fusion partner and that tumor protection can be induced.

Abstract: “Black holes” in the genomes of bacterial pathogens represent deletions of “anti-virulence” genes, i.e. genes that are detrimental to a pathogenic lifestyle. Identification of the missing genetic loci in the “black hole” identifies genes that are incompatible with the bacteria's pathogenicity. These genes, their gene products, and compounds generated by the enzymatic action of these gene products represent potential new compounds that are inhibitory to the bacterial pathogen and thus useful as pharmaceuticals. The utility of this concept is demonstrated in the missing gene for lysine decarboxylase, and the resulting inhibitory activity of cadaverine (the diaminoalkyl reaction product of lysine decarboxylase) on the Shigella enterotoxins. Diaminoalkyl compounds are therefore potent inhibitors of E. coli and Shigella spp. enterotoxins. Lysine decarboxylase generated from the gene cadA results in attenuation of the enterotoxic effects.

Abstract: A method is provided for the formation of liposomes of 0.1 &mgr;m to 50 &mgr;m in diameter having unilamella or multilamella structure and containing water insoluble or undissolved particulate materials comprising (a) forming liposomes and removing substantially all of any organic solvent used in their preparation, (b) freeze drying the liposomes so formed and then (c) rehydrating them in intimate admixture with the particulate material. Preferred encapsulated materials are particulate materials, most preferably microorganisms, plant or animals cells or water insoluble structures having organic solvent labile biochemical or immunological activity, but any water insoluble particulate may be encapsulated using the method. For example, catalysts or drugs that are sparingly soluble may also be so incorporated such that slow release into the patient's body may be provided while release of detergents included in the many lipoome preparation protocols may be avoided.

Abstract: The invention pertains to adjuvant and vaccine compositions of monophosphoryl lipid A, sugar and optionally an amine based surfactant, which when frozen and thawed or lyophilized and reconstituted reform a colloidal suspension having a light transmission of greater than or equal to 88% as measured spectrophotometrically.

Abstract: This application relates to the use of attenuated prokaryotic miccrooganism strains (such as Salmonella) expressing nucleic acid encoding HPV proteins as vaccines against HPV infection and the associated increased risk of cancer. In particular, the work shows that it is possible to assemble VLPs in a prokaryotic organism and that nasal immunization of mice with the strains HPV-specific conformationally dependent and neutralizing antibodies in serum and genital secretions. The experiments described herein show that it is also possible to assemble chimeric VLPs of a HPV including a fusion partner and that tumour protection can be induced.

Abstract: The present invention relates to Salmonella bacteria for use as a vaccine. The invention also relates to vaccines based thereon that are useful for the prevention of microbial pathogenesis. Further, the invention relates to the use of such bacteria or the manufacture of such vaccines. Finally, the invention relates to methods for the preparation of such vaccines.

Abstract: A novel composition comprising Invaplex from gram-negative bacteria is described and is effective as a vaccine against gram-negative bacterial infection.

Abstract: A live non-virulent vaccine composition and method for preparing the same comprising a virulent microorganismal strain which contains at least two mutations, wherein the first mutation results in an auxotrophic mutant which requires for proliferation, a nutrient which is normally available in the host tissues in an amount required by the auxotrophic mutant for proliferation and the second mutation results in the inability of the auxotrophic mutant to specifically transport the required nutrient from host-tissues into the auxotrophic mutant thereby producing an attenuated strain.

Abstract: This application relates to the use of attenuated prokaryotic miccrooganism strains (such as Salmonella) expressing nucleic acid encoding HPV proteins as vaccines against HPV infection and he associated increased risk of cancer. In particular, the work shows that it is possible to assemble VLPs in a prokaryotic organism and that nasal immunization of mice with the strains HPV-specific conformationally dependent and neutralizing antibodies in serum and genital secretions. The experiments described herein show that it is also possible to assemble chimeric VLPs of a HPV including a fusion partner and that tumor protection can be induced.

Abstract: The present invention relates generally to modified microorganisms suitable for use as live in ovo vaccines for avian species. The live in ovo vaccines of the present invention are useful for inducing immunity before or immediately after hatching against a virulent form of the modified microorganism or a microorganism immunologically related to the modified microorganism or a virulent organism or virus carrying an antigenic determinant expressed by the modified microorganism in the live vaccine. The subject live in ovo vaccines are particularly efficacious in enhancing the survival rate of newly-hatched poultry birds.

Abstract: Liposome encapsulated antibiotic therapy has limited application against infectious organisms, which can sequester in non-phagocytic cells. Virulence factors of these infectious organisms, for example bacterial components, when used in the formulation of liposomes can enhance the effectiveness of liposomes as delivery systems in the treatment of disease. In this manner, multi-functional liposomes can be developed to treat target diseases. In addition to serving as antibiotic delivery systems, such liposomes also have an immunization effect. Thus, the liposomes can be used for both the prevention and treatment of diseases.

Abstract: A vaccine strain OU5758 is provided which includes an attenuated immunogenic plasmidless Salmonella enterica serovar-Typhimurium strain OU5046 harboring a recombinant plasmid pOU1500 for immunizing a chicken against leucocytozoonosis. The strain OU5046 is adapted to remain substantially avirulent, survive in vivo for at least a number of days, colonize within the chicken's liver, spleen, ovaries, or other internal organs, and express foreign antigens. The recombinant plasmid pOU1500 contains a gene encoding the circumsporozoite protein of the sporozoite of the chicken leucocytozoonosis parasite Leucocytozoon caulleryi. The vaccine strain OU5758 containing pOU1500 is capable of expressing circumsporozoite protein of L. caulleryi sporozoite, inducing anti-L. caulleryi immunity in chickens when ingested, reducing the frequency and severity of the disease's occurrence, and thereby enabling the chicken to maintain its normal egg production.

Abstract: Attenuated Salmonella mutants which constitutively express the Vi antigen are disclosed, as well as vaccines against typhoid fever containing the same, live vector vaccines containing the same, and DNA-mediated vaccines containing the same.