Abstract: A composition and method for immunizing a mammal infected with Mycobacterium are disclosed. The genes gcpE, pstA, kdpC, papA2, impA, umaA1, fabG2_2, aceAB, mbtH2, lpqP, map0834c, cspB, lipN, or map1634 of M. paratuberculosis and their products that they encode are vaccine targets for Johne's and Crohn's disease. Eighteen M. paratuberculosis-specific genomic islands (MAPs) were identified. Three inverted large genomic fragments in M. paratuberculosis (INV) were also identified. These genomic identifiers represent novel virulence determinants that can be used as targets for vaccines and for developments of drugs against Johne's disease. The method can be used to deliver an immunizing compounds to a mammal, to provide an immune response against Johne's or Crohn's disease in the mammal.

Abstract: A method for producing isoprene includes culturing E. coli, which has isoprene productivity and in which a gene encoding a recA protein is attenuated or deleted, in a medium containing a carbon source. Therefore, a great amount of isoprene may be produced within a short period of time, and thereby considerably decreasing isoprene production unit costs.

Abstract: The present disclosure relates to genetically modified strains of Salmonella, engineered to be tumor navigating, self-eradicating, and armed with TRAIL to trigger tumor cell apoptosis. Also provided herein are methods of producing and methods of using such genetically modified Salmonella strains to treat cancer.

Abstract: Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.

Abstract: The present invention refers to new glycoconjugate antigens expressing built-in multiple epitopes and to polyvalent glycoconjugate vaccines intended for the protection of mammalians, and particularly for the protection of the human population from enteropathogenic bacteria, such as the Gram-positive anaerobic bacterium Clostridium difficile and the Gram-negative bacteria Salmonella typhi, Escherichia coli, Vibrio cholerae, Shigella flexneri, Salmonella typhimurium, Salmonella enteritidis, Salmonella paratyphi A, Shigella sonnei, Shigella dysenteriae, Salmonella cholerasuis, Klebsiella, Enterobacter, Pseudomonas aeruginosa and/or from viral gastrointestinal infections due to human noroviruses.

Abstract: A composition comprising intact killed bacterial cells that contain a therapeutic nucleic acid, a drug or a functional nucleic acid is useful for targeted delivery to mammalian cells. The targeted delivery optionally employs bispecific ligands, comprising a first arm that carries specificity for a killed bacterial cell surface structure and a second arm that carries specificity for a mammalian cell surface receptor, to target killed bacterial cells to specific mammalian cells and to cause endocytosis of the killed bacterial cells by the mammalian cells. Alternatively, the delivery method exploits the natural ability of phagocytic mammalian cells to engulf killed bacterial cells without the use of bispecific ligands.

Abstract: The subject application provides a genetically modified recombinant facultative intracellular invasive bacterial pathogen (RFIIBP) or a recombinant attenuated Salmonella vaccine (RASV) strains encoding Zika virus (ZIKV) antigens. These strains exhibit high immunogenicity, complete safety, and attenuation, and are unable to persist or be shed in an infective or viable form. These RFIIBPs and RASVs also exhibit regulated delayed attenuation in vivo, regulated delayed in vivo synthesis of protective ZIKV antigens. Methods of inducing mucosal, systemic and cellular immunities in hosts are also provided and antibodies produced using the disclosed RFIIBPs and RASVs can comprise neutralizing antibodies against ZIKV that do not crossreact with Dengue virus (DENV).

Abstract: The present invention relates to methods and compositions for identifying subjects treated with or considered for treatment with checkpoint blockade therapeutic agents that are at higher or lower risk for developing checkpoint therapy associated colitis, by analyzing the intestinal microbiome of those subjects. It is based, at least in part, on the discovery that the abundance of certain intestinal microbiota of the phyla Bacteroidetes, including the bacteria in the families Bacteroidaceae, Rikenellaceae, and Barnesisllaceae, and/or an increase or decrease in microbial genetic pathways involved in polyamine transport and/or B vitamin biosynthesis (e.g., (riboflavin (B2), pantothenate (B5) and thiamine (B1)) are associated with the likelihood of developing checkpoint therapy associated colitis.

Abstract: Provided herein are immunogenic compositions comprising a recombinant modified vaccinia virus Ankara (MVA) comprising a nucleic acid sequence encoding a CD40 ligand (CD40L) and a nucleic acid sequence encoding a heterologous disease-associated antigen, wherein the immunogenic composition induces increases T-cell immune responses specific for the heterologous disease-associated antigen when administered to a human host, and related methods and uses.

Abstract: The present invention concerns a composition comprising at least one prophylactically or therapeutically active agent selected from the group consisting of attenuated Porphyromonas gingivalis, inactivated Porphyromonas gingivalis, a subunit of Porphyromonas gingivalis, a recombinant or isolated immunogenic polypeptide or peptide from Porphyromonas gingivalis or a c DNA from Porphyromonas gingivalis, for use as a vaccine for preventing or treating periodontitis, diabetes, obesity and/or complications thereof in a subject. The present invention also concerns an isolated antibody having specificity for Porphyromonas gingivalis for use for preventing or treating periodontitis, diabetes, obesity and/or complications thereof in a subject.

Abstract: General secretory pathway (GSP) mutant Listeria bacteria are provided. Aspects of the bacteria include the presence of a GSP mutation, e.g., a SecY and/or SecA mutation. Also provided are methods of making and using the Listeria bacteria comprising a GSP mutation as vectors and vaccines expressing a heterologous nucleic acid.

Abstract: The invention provides compositions and methods for using PltA, PltB, CdtB, or a mutant thereof, in inducing or enhancing an immune response.

Abstract: Microorganisms comprising a maltose-inducible promoter and methods of use in producing biologics and introducing biologics to sites in a maltose-dependent manner. The microorganisms include a maltose-inducible promoter operably connected to a coding sequence of a biologic. The biologic may be a polypeptide or a nucleic acid. Polypeptide biologics may include lytic proteins and/or secreted proteins. Nucleic acid biologics may include antisense RNA, other types of RNA, or other types of nucleic acids. The microorganisms can be used to produce the biologics and/or introduce the biologics to in vitro or in vivo sites in a maltose-dependent manner. The microorganisms can also be used in maltose-dependent gene silencing.

Abstract: The present invention provides Listeria vaccine strains that express a heterologous antigen and a metabolic enzyme, and methods of generating same.

Abstract: Compositions and methods directed to ESAT-6 variants which serve as vaccines for the prevention and prophylactic treatment of TB.

Abstract: Vaccines and compositions containing an attenuated L. monocytogenes prsA2 htrA deletion mutant for use in the presentation of foreign or exogenous antigens and in the treatment or prevention of diseases such as cancer or infectious disease are provided.

Abstract: The present invention includes a method of observing and evaluating bacterial infections within the lymph nodes of animals presented for harvest comprising: inoculating at one or more sites of an animal a known amount of a pathogen, wherein the one or more inoculation sites comprise lymph node drainage areas, and at one or more time points obtaining one or more lymph node biopsies to determine the extent of the pathogen in the lymph nodes.

Abstract: The present invention provides methods of treating, protecting against, and inducing an immune response against a human papillomavirus-associated oropharyngeal tumor or cancer, comprising the step of administering to a subject a recombinant Listeria strain expressing a human papillomavirus antigen.

Abstract: The present invention relates to inducing acid resistance in a bacterium and methods of increasing the acid resistance of an acid sensitive bacterium.

Abstract: The present invention relates to gram positive bacteria with increased stress resistance and/or improved storage characteristics. In particular, the invention relates to gram positive bacterium which accumulate intracellular trehalose. The gram positive bacterium according to the invention lack cellobiose-specific PTS system IIC component (PtcC) activity. The gram positive bacterium may further lack trehalose 6-phosphate phosphorylase (TrePP) activity. The gram positive bacterium may further overexpress trehalose transporters. The invention further relates to compositions comprising such gram positive bacterium as well as methods and uses thereof.

Abstract: The invention relates to compositions and methods for making and using recombinant bacteria that are capable of regulated attenuation and/or regulated expression of one or more antigens of interest.

Abstract: Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.

Abstract: Recombinant Bordetella pertussis strains derived from parent strain Tohama are provided. The new strains are obtained by homologous recombination using a allelic exchange vector pSS4245, which allows the replacement of sections of the bacterial chromosome without leaving any accessory mutations. The segment encoding PT subunit S1 is replaced to introduce two mutations causing inactivation of the toxic activity of PT. This strain can be further modified to express increased amounts of rPT and/or PRN. A second copy of the ptx cluster of the five PT structural genes of the ptx-ptl operon with their promoter and the ptl terminator and containing the above mutations can be inserted elsewhere on the chromosome. In addition, a second copy of the PRN gene can be inserted on the chromosome. In both cases, abandoned gene loci are selected as the insertion site to avoid the introduction of unwanted genetic alterations.

Abstract: Described herein are microorganisms that are modified so that they have an increased ability to be recognized by the innate immune system of a eukaryote, relative to an unmodified microorganism. A microorganism may be a gram-negative bacterium that has been modified to produce high potency lipopolysaccharide, e.g., Yersinia pestis expressing LpxL. Such modified microorganisms may be used as vaccines for protection against an infection by the unmodified microorganism. They may also be used as delivery vehicles of one or more heterologous antigens, e.g., antigens from pathogens or those associated with a hyperproliferative eukaryotic cell.

Abstract: The present invention is related to a combination comprising a first constituent and a second constituent, wherein the first constituent is a bacterial cell which comprises at least one recombinant nucleic acid molecule encoding a phagolysosomal escape peptide or polypeptide; and wherein the second constituent is a biologically active agent. In certain embodiments, the combination is of use as a vaccine to induce an immune response in a mammal.

Abstract: The present invention encompasses a recombinant Yersinia pestis bacterium and a vaccine comprising a recombinant Yersinia pestis bacterium.

Abstract: The invention encompasses a recombinant bacterium capable of eliciting an immune response against Streptococcus pneumoniae, a vaccine comprising the bacterium, and methods of using the bacterium.

Abstract: The present invention encompasses recombinant bacteria and immunogenic compositions comprising the bacteria. The immunogenic composition may be used to induce an immune response against C. perfringens.

Abstract: The invention relates to prokaryotic expression cassettes comprising a stress-regulated promoter, the promoter of the GroESL operon of Lactococcus lactis. Said cassettes can be used for the expression of genes of interest in gram-positive bacteria, and especially for producing and releasing a protein of interest when the bacteria are administered to an individual.

Abstract: The present invention is based on the finding that microorganisms can be modified so as to express certain factors important in generating or raising host immune responses. In particular, the invention provides modified microorganisms which, when subjected to conditions which would be expected to suppress or reduce the expression, function and/or activity of certain factors, exhibit increased (often significantly increased) expression, function and/or activity of those factors. The invention provides a modified microorganism capable of expressing at least one factor under conditions in which a wild-type (or unmodified) strain of the same microorganism, exhibits inhibited expression of the at least one factor.

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: The present invention provides Listeria vaccine strains that express a heterologous antigen and a metabolic enzyme, and methods of generating same.

Abstract: Provided herein are prime-boost regimens and materials used therein. The prime-boost regimens enhance the immune response to a target antigen. The vaccines used for boost are comprised of recombinant attenuated metabolically active Listeria that encodes an expressible antigen that is cross-reactive with the target antigen. In some examples, the immune response is a cellular immune response.

Abstract: This invention provides compositions and methods for treating and vaccinating against an Her2/neu antigen-expressing tumor and inducing an immune response against dominant in a non-human animal.

Abstract: This invention provides methods and compositions for using a live attenuated Listeria for inhibiting cell-mediated suppression of anti-disease infiltrating T lymphocytes in a subject having the disease.

Abstract: The present invention relates to a means of controlling infection persistence of Helicobacter pylori (H. pylori). In particular, the present invention relates to an isolated, genetically modified Helicobacter pylori comprising a functional urease, wherein the contiguous amino acid sequence between amino acid 529 and amino acid 555 of SEQ ID NO:1 is altered to produce said modified Helicobacter pylori which is unable to establish or maintain a persistent infection.

Abstract: The present invention provides recombinant Listeria strains comprising an angiogenic factor, recombinant polypeptides comprising an angiogenic factor operatively linked to a polypeptide comprising a PEST-like sequence, recombinant nucleotide molecules encoding same, related vaccines, and immunogenic and therapeutic methods utilizing same.

Abstract: Therapeutic methods for cancer treatments using a combined prokaryotic-eukaryotic delivery and expression system for the delivery of multiple therapeutic factors via a modified tumor-targeted bacteria. A targeted bacteria-vector system elicits an inter-kingdom dual expression (IKDE) of antitumor agents, in the nucleus or cytoplasm of eukaryotic cells, with priming and maintenance of the vector in the bacterium. The therapeutic factors include small interfering RNAs, tumoricidal proteins, DNA molecules, or a combination thereof. The system provides direct killing of tumor cells and alters the tumor microenvironment by expressing anti-angiogenic factors and cytokines in intracellular and/or extracellular environments. Also provided are methods of using natural exosomes comprising cargoes obtained from the bacterially infected cells. The bacteria-vector system is useful for many types of tumor and cancer as well as recombinant vaccines.

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: 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 relates to a probiotic cell transformed with a construct suitable to overexpress and display on the surface of the probiotic cell a fusion protein comprising at least a portion of a transport protein coupled to at least a portion of one or more antigenic proteins or peptides. Probiotic-derived vesicles displaying this fusion protein as well as methods of inducing an immune response using the probiotic cells or vesicles are also disclosed.

Abstract: The present invention provides a recombinant bacterium and methods of using the recombinant bacterium to induce a cellular immune response.

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: 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 0 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: The present disclosure generally relates to genetic engineering of bacteria. More particularly, the present disclosure relates to genetic engineering of Gram-negative bacteria expressing different species of lipid A on their surface. In one embodiment, the present disclosure provides for an engineered strain of E. coli according to Table 1. In another embodiment, the present disclosure provides for a lipopolysaccharide purified from an engineered strain of E. coli according to Table 1.

Abstract: The present invention relates to gram-negative bacterial mutants resistant to one or more stress conditions, including, but not limited to, CO2, acid pH, and high osmolarity. The present invention also relates more particularly to gram-negative bacterial mutants with reduced TNF-? induction having a mutation in one or more lipid biosynthesis genes, including, but not limited to msbB, that are rendered stress-resistant by a mutation in the zwf gene. The present invention provides compositions comprising one or more stress-resistant gram-negative bacterial mutants, preferably attenuated stress-resistant gram-negative bacterial mutants. In particular, the present invention relates to methods for prophylaxis or treatment of a virally induced disease in a subject comprising administering to said subject one or more stress-resistant gram-negative bacterial mutants, preferably attenuated stress-resistant gram-negative bacterial mutants.

Abstract: Recombinant immunogenic compositions, and methods for the manufacture and use, are provided for the prevention and treatment of intracellular pathogen diseases in humans and animals. The recombinant immunogenic compositions express high levels of recombinant proteins in vectors that do not harbor an antibiotic resistance marker (“unmarked”).

Abstract: Mycobacterium bovis BCG is a potent stimulator of the cellular immune response and has potential as a recombinant vaccine vector. Disclosed are BCG strains that generate greater MHC class I presentation of a transgenic protein, relative to the unmutated parental strain, and that improve a recipient's CD8+ T cell response against the transgenic protein following vaccination. The mycobacterial constructs and their respective t/ansposon mutant BCG strains exhibit increased immunogenicity that is several times greater than responses generated by the parental strain and other existing modified rBCG strains. Furthermore, upon introducing the SIV gag gene into these novel strains, we observed that these strains primed for increased CD8+ T cell responses in a heterologous prime/boost regimen, comparable to levels generated by plasmid DNA vaccines. Creation of a second generation rBCG vector that may be utilized as a vaccine vector for immunizing against a variety of pathogens.

Abstract: The present invention provides Listeria vaccine strains that express a heterologous antigen and a metabolic enzyme, and methods of generating same.

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.