Abstract: Immunogenic compositions imparting dual protection against enterotoxigenic labile toxin (LT)-expressing Escherichia coli (ETEC) and Vibrio cholerae based on the hyperexpression of recombinant cholera toxin B antigen by attenuated, live bacterial vectors derived from Vibrio cholerae are disclosed. The compositions exhibit dual immunogenicity and retain the ability to colonize gastrointestinal mucosa-associated lymphoid tissues.

Abstract: A live bacterium, having a DNA construct stabilized against transduction of other bacteria, having a promoter sequence and encoding a fusion peptide, comprising a bacterial secretion peptide portion and a non-bacterial immunogenic polypeptide portion, having a nucleotide sequence coding for the non-bacterial immunogenic polypeptide portion which has at least one codon optimized for bacterial expression. The bacterium has a secretion mechanism which interacts with at least the bacterial secretion peptide portion to cause a secretion of the fusion peptide from the bacterium, and a genetic virulence attenuating mutation. The bacterium is adapted to act as an animal vaccine, to transiently infect a tissue of the animal, and cause an immunity response to the non-bacterial immunogenic polypeptide portion in the animal to a non-bacterial organism associated with the non-bacterial immunogenic polypeptide portion.

Abstract: The present invention provides methods and compositions for production of gram-negative bacterial mutants that are defective in intestinal colonization capacity and sensitive to infection by bacteriophage P1. Thus the present invention provides immunogenic compositions for the prevention or attenuation of food- and water-borne illnesses associated with ingestion of bacteria such as enterohemorrhagic Escherichia coli.

Abstract: A bioengineering, in particular to develop novel probiotic preparations based on Bacillus-strain bacteria, which can be used for preventing and treating infectious diseases and disbiosis of a human being, farm animals and birds. The novel strains of B. subtilis 07 (VKPM No. B-8611) and B. licheniformis 09 (VKPM No. B-8610) exhibit a broad spectrum of antagonistic activity, high proteolytic and amylase activity and a distinct ability in terms of a lysozim production. Such strains do not compete with each other but enter into synergistic relations in the form of an increased antagonistic action of the biopreparation. The inventive biopreparation comprises the B. subtilis 07 VKPM No. B-8611 and B. licheniformis 09 VKPM No. B-8610 strains and a protective medium. Such biopreparation can also contain a solvent and/or filler and exhibits an increased antagonistic activity with respect to a wide range of pathogenic and opportunistic pathogenic microorganisms and a resistance to quite a number of antibiotics.

Abstract: The invention relates to Salmonella typhi Ty21a comprising core-linked Shigella dysenteriae serotype 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 Shigella dysenteriae serotype 1 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: The present invention describes an immunogenic formulation to be used in mammals against the respiratory syncytial virus (RSV), consisting in the Calmette-Guérin bacillus (BCG) strain or other attenuated Mycobacterium strain that expresses heterologously at least one protein or immunogenic fragment of the RSV subtype A or RSV subtype B strains, originated from proteins NS1, NS2, N, P, M, SH, M2 (ORF1), M2 (ORF2), L, F or G. The genetic material that encodes for these proteins or immunogenic fragments is inserted into the BCG genome or extrachromosomally in one or several copies, which expression is regulated by endogenous or exogenous BCG promoters, either constitutive or inducible. The viral proteins or immunogenic fragments can be expressed by BCG as cytoplasmic-soluble, extracellularly-secreted or cell membrane-bound proteins. The preparation can further contain combinations of previously described formulations. The formulation can be stabilized by freeze-drying (conservation range from 4° C. and 25° C.

Abstract: A genetically modified strain of M. tuberculosis or Mycobacterium bovis BCG is provided, wherein the genetically modified strain comprises at least one modified sequence comprising SEQ ID NO: 1, SEQ ID NO: 2, or both, having at least one mutation at T2, Q4, F8, A14, L28, L29, W43, G45, Y51, Q55, Q56, N66, M83, V90, M93, or F94 in SEQ ID NO:1; or at least one mutation at Q3, F7 A13, L27, W42, G44, Y50, Q54, N65, N67, M82, V89, M92, or F93 in SEQ ID NO:2, or a deletion at the terminal end of less than 20 amino acids. In a preferred embodiment, the mutation is at least one of T2H, Q4L, F8I, AI4R, L28A, L29S, W43R, G45T, Q55I, Q56A, N66I, N67A, M83I, V90R, M93T, or F94Q in SEQ ID NO:1, and Q3L, F7I, A13R, L27A, L28S, W42R, Q44T, Q54I, N65I, M82I, V89R, M92T, and F93Q in SEQ ID NO:2. Similarly, the genetically modified strain may also secrete ESAT-6 with a hexa-histidine tag, tetra-cysteine tag, or FLAG-tag, a GFP-fusion, or a short truncation at the C-terminal end of less than 20 amino acids.

Abstract: Disclosed herein are methods for inducing an immunological CTL response to an antigen by sustained, regular delivery of the antigen to a mammal so that the antigen reaches the lymphatic system. Antigen is delivered at a level sufficient to induce an immunologic CTL response in a mammal and the level of the antigen in the mammal's lymphatic system is maintained over time sufficient to maintain the immunologic CTL response. Also disclosed is an article of manufacture for delivering an antigen that induces a CTL response in an animal.

Abstract: The invention relates to an immunogenic composition composed of secreted polypeptides derived from Campylobacter jejuni non-flagellar proteins that are coordinately expressed with the flagellar regulon. The invention also relates to a method of inducing an immune response to the non-flagellar protein polypeptides.

Abstract: According to the present invention, there is provided a means of expressing and displaying a protein on the cell surface of a bifidobacterium. In the gene for expressing a protein on the surface of a bifidobacterium of the present invention, a gene coding for a bifidobacterium-derived GNB/LNB substrate-binding membrane protein and a gene coding for the target protein or peptide are linked in this order from the 5? end side. Thus, a bifidobacterium transformed by introducing the gene for expressing a protein on the surface of a bifidobacterium of the present invention expresses the target protein or peptide on the surface thereof. When the target protein or peptide is an antigen protein or an antigen peptide, the transformed bifidobacterium of the present invention is useful as an oral vaccine.

Abstract: The invention provides for anti-pathogen vaccines produced in recombinant bacteria and/or transgenic plants and administered through standard vaccine introduction methods or oral administration. In one embodiment, the vaccine is administered through the consumption of the edible plant as food, or the bacteria administered orally. The present invention also provides a method of using genetically modified microorganisms, such as lactic acid bacteria, including Lactococcus lactis strains, as oral vaccines. In one embodiment, Lactococcus lactis expressing the avian influenza HA gene can be used as an oral vaccine for protection against H5N1 virus infection. In another embodiment, said Lactococcus lactis is administered as an oral vaccine in conjunction with an adjuvant such as cholera toxin B.

Abstract: The present invention encompasses a recombinant bacterium comprising a regulated rfaH nucleic acid, as well as a vaccine comprising said recombinant bacterium. Other embodiments of the present invention encompass a recombinant bacterium comprising a regulated rfaH nucleic acid and a regulated rfc nucleic acid, while additional embodiments encompass a recombinant bacterium comprising a regulated rfaH nucleic acid and at least one nucleic acid encoding at least one exogenous antigen.

Abstract: The invention relates to Salmonella typhi Ty21a comprising core-linked Shigella dysenteriae serotype 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 Shigella dysenteriae serotype 1 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: Site-specific Listeria integration vectors and methods for their use are provided. The subject vectors include a bacteriophage integrase gene and a bacteriophage attachment site, where in many embodiments the bacteriophage that is the source of these elements is a listeriophage. In certain embodiments, the subject vectors further include a multiple cloning site, where the multiple cloning site may further include a polypeptide coding sequence, e.g., for a heterologous antigen. The subject vectors and methods find use in a variety of different applications, including the study of Listeria species and the preparation of Listeria vaccines.

Abstract: Disclosed and claimed are a mutant of a gram negative bacterium, wherein said bacterium has at least one mutation in a nucleotide sequence which codes for a polypeptide having an identity which is equal or more than 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% with an amino acid sequence coded by a nucleotide sequence selected from the group consisting of nucleotide sequences identified SEQ ID NO: 2, 6, 9, 12, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55, 58, 61, 64, 67, 70, 75, 78, 81, 84, 87, 90, 93; said mutation resulting in attenuated virulence of the bacterium. Immunogenic compositions and vaccines containing such a mutant are also disclosed and claimed.

Abstract: The invention relates to a multivalent Clostridium difficile vaccine comprising a Salmonella Typhi live vector comprising the cell binding domain of TcdA toxin (CBD/A) of Clostridium difficile or an antigenic fragment thereof and the cell binding domain of TcdB toxin (CBD/B) of Clostridium difficile or an antigenic fragment thereof and optionally the cell-binding subunit component (CdtB) of binary toxin of Clostridium difficile or an antigenic fragment thereof. The invention further provides methods of inducing an immune response and methods of preventing recurrence of C. difficile infections in subjects.

Abstract: Provided herein are vaccine vectors including an antigenic polypeptide and an HMGB1 polypeptide present on the surface of the vaccine vector. Compositions comprising the vaccine vectors are also provided and include a pharmaceutically acceptable carrier, suitably a carrier for oral or nasal administration. Also provided are methods of enhancing immune responses, in particular antibody immune response and suitably an IgA response, by administering the vaccine vectors or compositions disclosed herein to a subject.

Abstract: The invention concerns a methylated immunogenic recombinant peptide sequence comprising mycobacterial heparin-binding hemagglutinin. The invention also concerns chemical and enzymatic methods for preparing such a sequence, the sequence being previously produced in a non-methylated recombinant form then methylated by post-translational modification. The invention further concerns recombinant tools, vectors and host cells for implementing post-translational enzymatic methylation of the recombinant HBHA. The invention finally concerns immunogenic compositions comprising methylated, native or recombinant HBHA, such compositions being useful for preparing vaccines against mycobacterial infections.

Abstract: In one embodiment, the present invention provides for an edible mini-capsule form of live, non-persisting, recombinant Lactococcus lactis (L. lactis) vaccine against a pathogen such as the highly virulent influenza H5N1 strain. Enteric coated capsule of the present invention induced high levels of hemagglutinin-specific serum IgG and fecal IgA antibody production after oral administration in mice and chickens, and rendered complete protection against a lethal challenge of H5N1 virus in mice. The present invention thus demonstrates a broadly applicable platform technology for producing and administering edible vaccines against bacterial and viral infections.

Abstract: Immunogenic compositions comprising recombinant intracellular pathogens that have been transformed to express recombinant immunogenic antigens of the same or other intracellular pathogens and immunostimulatory molecules are provided. Exemplary immunogenic compositions include, but are not limited to, recombinant BCG expressing Mycobacteria major extracellular proteins and immunostimulatory molecules.

Abstract: Oral immunogenic compositions imparting dual protection against enterotoxigenic labile toxin (LT)-expressing Escherichia coli (ETEC) and Vibrio cholerae based on the delivery of recombinant cholera toxin B antigen by attenuated, live bacterial vectors derived from Vibrio cholerae are disclosed. The compositions exhibit dual immunogenicity and retain the ability to colonize gastrointestinal mucosa-associated lymphoid tissues.

Abstract: The present invention relates to DNA sequences encoding Vmp-like polypeptides of pathogenic Borrelia, the use of the DNA sequences in recombinant vectors to express polypeptides, the encoded amino acid sequences, application of the DNA and amino acid sequences to the production of polypeptides as antigens for immunoprophylaxis, immunotherapy, and immunodiagnosis. Also disclosed are the use of the nucleic acid sequences as probes or primers for the detection of organisms causing Lyme disease, relapsing fever, or related disorders, and kits designed to facilitate methods of using the described polypeptides, DNA segments and antibodies.

Abstract: This invention provides recombinant polypeptides comprising a fragment of a High Molecular Weight Melanoma-Associated Antigen (HMW-MAA), recombinant Listeria strains comprising same, and methods of inducing an anti-HMW-MAA and anti HER-2/neu immune response thus treating and impeding the growth of tumors, comprising administering same.

Abstract: Compounds and methods for the diagnosis and treatment of Chlamydial infection are disclosed. The compounds provided include polypeptides that contain at least one antigenic portion of a Chlamydia antigen and DNA sequences encoding such polypeptides. Pharmaceutical compositions and vaccines comprising such polypeptides or DNA sequences are also provided, together with antibodies directed against such polypeptides. Diagnostic kits containing such polypeptides or DNA sequences and a suitable detection reagent may be used for the detection of Chlamydial infection in patients and in biological samples.

Abstract: This invention provides recombinant polypeptides comprising a fragment of a High Molecular Weight Melanoma-Associated Antigen (HMW-MAA), recombinant Listeria strains comprising same, and methods of inducing an immune response and treating and impeding the growth of tumors, comprising administering same.

Abstract: A method of inhibiting endothelial cell proliferation in a mammal is provided. The method comprises the step of administering to the mammal an effective immunological response eliciting amount of a DNA composition comprising a DNA construct operably encoding a VEGF receptor polypeptide and a pharmaceutically acceptable carrier therefor, whereby said mammal exhibits an immune response elicited by vaccine and specific to proliferating endothelial cells. The methods of this invention inhibit vascular endothelial cell proliferation in the tumor micro-environment. Angiogenesis inhibition and subsequent decrease in tumor growth and dissemination is achieved.

Abstract: Helicobacter based preparations comprising a pharmacologically active molecule of interest are disclosed, as well as methods of preparing and using said preparations. In particular, Helicobacter pylori vectors, vector plasmids and recombinant cells that include a sequence encoding a pharmacologically active molecule of interest useful in therapeutic treatments and/or vaccination against disease are provided. Delivery of the pharamacologically active molecules is provided at the mucosal surface, such as the gastric mucosa or nasal membranes, to provide effective and continuous delivery of a pharmacologically active agent. In some embodiments, the Helicobacter provides exposure of a desired molecule of interest though the surface of the Helicobacter, providing exposure of the antigen to the host at the gastric mucosa. Live Helicobacter pylori vaccines are also provided. Vectors and shuttle vector constructs of the Helicobacter are also disclosed.

Abstract: The invention is directed to an episomal recombinant nucleic acid encoding at least two heterologous antigens each fused to a PEST-endogenous polypeptide, vaccines comprising the same, methods of preparing same, and methods of inducing an immune response, and treating, inhibiting, or suppressing cancer or tumors comprising administering the same.

Abstract: The invention provides a bacterium containing a polynucleotide comprising a nucleic acid encoding a heterologous antigen, as well as fusion protein partners. Also provided are vectors for mediating site-specific recombination and vectors comprising removable antibiotic resistance genes.

Abstract: The present invention relates generally to the production, purification, and isolation of human growth hormone (hGH). More particularly, the invention relates to the production, purification, and isolation of substantially purified hGH comprising non-naturally encoded amino acids and hGH from recombinant host cells or culture medium including, for example, yeast, insect, mammalian and bacterial host cells. The process of the present invention is also useful for purification of hGH linked to polymers or other molecules.

Abstract: Single-dose controlled-release immunogenic formulations, such as vaccines, based on bioerodible polyanhydride copolymer or homopolymer microparticles for the control of immune response mechanisms are provided. The copolymer or homopolymer microparticles degrade by surface-erosion from in vivo hydrolysis of anhydride linkages at the surface of the microparticle, which results in controlled release of immunogen(s) to a patient.

Abstract: The present invention includes cold-adapted, acid-fast bacterium for use as a vaccine and a vaccine vector. In preferred embodiments, the cold-adapted, acid-fast bacterium is a Mycobacteria, for example, Mycobacteria shottsii.

Abstract: The present invention relates to Salmonella enterica comprising at least one pgl operon of Campylobacter jejuni or a functional derivative thereof and presenting at least one N-glycan of Campylobacter jejuni or N-glycan derivative thereof on its cell surface. In addition, it is directed to medical uses and pharmaceutical compositions thereof as well as methods for treating and/or preventing Campylobacter and optionally Salmonella infections and methods for producing these Salmonella strains.

Abstract: The present invention provides compositions and methods for delivery of one or more hepatitis C virus (HCV) antigens using a bacterium recombinantly encoding and expressing such antigens. In certain embodiments, the bacterial platform comprises the use of attenuated and killed but metabolically active forms of Listeria monocytogenes.

Abstract: Immunogenic compositions comprising growth regulatable recombinant attenuated intracellular pathogens that have been transformed to express recombinant immunogenic antigens of the same or other intracellular pathogens are provided. Exemplary immunogenic compositions include, growth regulatable and growth limited recombinant attenuated intracellular pathogen immunogenic compositions.

Abstract: A method of detecting an immune response to a paratuberculosis-specific antigen, comprising incubating a sample from a subject with the paratuberculosis-specific antigen and detecting the presence of an antibody in the sample as an indication of an immune response to the paratuberculosis-specific antigen. The antigen may be obtained from a novel M. paratuberculosis strain JTC303. The antigen may be obtained from the JTC303 culture filtrate. Also provided are antibodies to the paratuberculosis-specific antigen, and a diagnostic kit for the detection of an immune response to a paratuberculosis-specific antigen in a mammal.

Abstract: The present invention relates to fusion proteins containing at least two Mycobacterium tuberculosis antigens. In particular, it relates to bi-fusion proteins which contain two individual M. tuberculosis antigens, tri-fusion proteins which contain three M. tuberculosis antigens, tetra-fusion proteins which contain four M. tuberculosis antigens, and penta-fusion proteins which contain five M. tuberculosis antigens, and methods for their use in the diagnosis, treatment and prevention of tuberculosis infection.

Abstract: The present invention provides an export signal system based on E. coli CS3 antigen for directing the secretion of foreign antigens from host cells. In particular, the invention describes genetic constructs encoding fusion proteins that contain a CS3 export signal fused to at least one heterologous amino acid sequence. Attenuated microorganisms expressing the fusion proteins and pharmaceutical compositions comprising such attenuated microorganisms are also disclosed.

Abstract: A live attenuated derivative of a pathogenic bacterium intended for use as a vaccine.

Abstract: Compositions and methods for protecting a susceptable host against an infection of Shigella sonnei are disclosed. Such compositions and methods are useful for protecting the host against bacillary dysentery and shigellosis.

Abstract: A method of inhibiting endothelial cell proliferation in a mammal is provided. The method comprises the step of administering to the mammal an effective immunological response eliciting amount of a DNA composition comprising a DNA construct operably encoding a VEGF receptor polypeptide and a pharmaceutically acceptable carrier therefor, whereby said mammal exhibits an immune response elicited by vaccine and specific to proliferating endothelial cells. The methods of this invention inhibit vascular endothelial cell proliferation in the tumor micro-environment. Angiogenesis inhibition and subsequent decrease in tumor growth and dissemination is achieved.

Abstract: The present invention provides methods of treating, protecting against, and inducing an immune response against cervical cancer, comprising the step of administering to a subject a recombinant Listeria strain, comprising a fusion peptide that comprises an LLO fragment and an E7 and/or E6 antigen. The present invention also provides methods for inducing an anti-E7 response in a human subject and treating HPV-mediated diseases, disorders, and symptoms comprising administration of the recombinant Listeria strain.

Abstract: This invention relates to solid formulations for the oral delivery of live microbial cells which comprise dried viable cells and small amounts of a bile acid binding agent, for example, an anion exchange resin such as cholestyramine. The presence of bile acid binding agents in the formulation significantly increases the survival of the cells in the intestinal tract and facilitates delivery of the viable cells to the intestine.

Abstract: The present invention relates to novel recombinant vaccines providing protective immunity against tuberculosis. Further, the present invention refers to novel recombinant nucleic acid molecules, vectors containing said nucleic acid molecules, cells transformed with said nucleic acid molecules and polypeptides encoded by said nucleic acid molecules.

Abstract: Attenuated microorganisms expressing Clostridium difficile antigen(s), and methods of using the same for vaccination of patients are disclosed The invention provides an attenuated microorganism expressing an immunogenic portion of a C difficile Toxin A C-terminal repeat region and/or a C difficile Toxin B C-terminal repeat region The microorganism is an attenuated Salmonella comprising an integrated gene expression cassette that directs the expression of the immunogenic peptide from an in vivo inducible promoter.

Abstract: The invention provides lipid A deficient mutant Neisseria meningitidis cells, pharmaceutical compositions incorporating such cells, and methods of using such cells.

Abstract: The present invention provides an oral vaccine against a bacterial infectious disease (e.g., typhoid fever, cholera, or dysentery). The oral vaccine of the present invention is a capsule formulation in which a transformed microorganism that expresses a flagellin antigen protein or that secretes a flagellin antigen protein out of the cell of the microorganism is encapsulated with an acid-resistant membrane. Examples of the microorganism include intestinal bacteria belonging to the genus Bifidobacterium, the genus Lactobacillus, the genus Lactococcus, and the like. The form of the capsule formulation may be any one of a seamless capsule formulation, a soft capsule formulation, and a hard capsule formulation.

Abstract: This invention relates to immunotherapeutic vaccine composition comprising an ISG15 tumor antigen and to methods of preventing and treating a tumor growth by using said immunotherapeutic composition.

Abstract: The present invention relates to DNA sequences encoding Vmp-like polypeptides of pathogenic Borrelia, the use of the DNA sequences in recombinant vectors to express polypeptides, the encoded amino acid sequences, application of the DNA and amino acid sequences to the production of polypeptides as antigens for immunoprophylaxis, immunotherapy, and immunodiagnosis. Also disclosed are the use of the nucleic acid sequences as probes or primers for the detection of organisms causing Lyme disease, relapsing fever, or related disorders, and kits designed to facilitate methods of using the described polypeptides, DNA segments and antibodies.

Abstract: The invention relates to Salmonella typhi Ty21a comprising core-linked Shigella dysenteriae serotype 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 Shigella dysenteriae serotype 1 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.