Abstract: Bacterial strains are provided having at least one of a reduced size, a sialic acid coat, inducibly altered surface antigens, and expression of PD-L1 or CTLA-4 antagonists and/or tryptophanase. The bacteria may have improved serum half-life, increased penetration into tumors, increased tumor targeting and increased antitumor activity. The bacteria are useful for delivery of therapeutic agents that treat of neoplastic diseases including solid tumors and lymphomas.

Abstract: Chimeric proteins are expressed, secreted or released by a bacterium to immunize against or treat a parasite, infectious disease or malignancy. The delivery vector may also be attenuated, non-pathogenic, low pathogenic, or a probiotic bacterium. The chimeric proteins include chimeras of, e.g., phage coat and/or colicin proteins, bacterial toxins and/or enzymes, autotransporter peptides, lytic peptides, multimerization domains, and/or membrane transducing (ferry) peptides. The active portion of the immunogenic chimeric proteins can include antigens against a wide range of parasites and infectious agents, cancers, Alzheimer's and Huntington's diseases, and have enhanced activity when secreted or released by the bacteria, and/or have direct anti-parasite or infectious agent activity. The activity of the secreted proteins is further increased by co-expression of a protease inhibitor that prevents degradation of the effector peptides.

Abstract: Bacterial strains are provided having at least one of a reduced size, a sialic acid coat, inducibly altered surface antigens, and expression of PD-L1 or CTLA-4 agonists and/or tryptophanase. The bacteria may have improved serum half-life, increased penetration into tumors, increased tumor targeting and increased antitumor activity. The bacteria are useful for delivery of therapeutic agents that treat of neoplastic diseases including solid tumors and lymphomas.

Abstract: Gram-negative bacterial mutants resistant to one or more stress conditions, including CO2, acid pH, and high osmolarity, and 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. Compositions are provided comprising one or more stress-resistant gram-negative bacterial mutants, preferably attenuated stress-resistant gram-negative bacterial mutants. Methods are provided for prophylaxis or treatment of a virally induced disease in a subject comprising administering to a subject a stress-resistant gram-negative bacterial mutants, preferably attenuated stress-resistant gram-negative bacterial mutants. The stress-resistant gram-negative bacterial mutants may serve as vectors for the delivery of one or more therapeutic molecules to a host.

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: 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: Bacteria which co-express protease inhibitors and protease sensitive therapeutic agents, which are surface displayed, secreted and/or released and result in their localized production and maintenance within a target tissue and inactivation outside of the target tissue, thereby increasing therapeutic activity and reducing the systemic toxicity. The bacteria may be attenuated, non-pathogenic, low pathogenic or a probiotic. Protease sensitivity may be further accomplished by engineering protease degradation sites within the therapeutic agents, further enhancing the inactivation outside of the target tissue while retaining activity within the target tissue through co-expression of a protease inhibitor. Novel chimeric proteins secreted by bacteria, including chimeric toxins targeted to neoplastic cells, tumor matrix cells and cells of the immune system, and combination therapies of these protease inhibitor:chimeric toxin-expressing bacteria together with small-molecule and biologic agents are also described.

Abstract: A host antigen-specific antibody testing system and method. The a ternary complex of the antigen, a ligand-bound anti-host IgM, and a non-host anti-antigen IgG detector conjugate selectively form a quaternary complex with host antibodies, wherein the host antibodies and IgG compete for the antigen, and the anti-host IgM binds the host antibodies. The quaternary complex is retained by an immobilized IgM ligand binding agent, and any residual ternary complex is retained by a later encountered immobilized anti-non-host IgG. If sufficient host antibodies have a high affinity for the antigen, the complex is detected at the quaternary complex detection region based on the presence of the detector, and if there are insufficient high affinity host antibodies, the ternary complex migrates past the quaternary complex detection region and is retained and detected at a control region.

Abstract: The present invention provides purified protease inhibitors derived from microorganisms alone or in combination with bacteriocins and/or antibodies. The protease inhibitors may also be expressed by microbiome or probiotic microorganisms alone or in combination with bacteriocins and/or antibodies. The invention also provides methods and compositions for improving the expression of endogenous or heterologous protease inhibitors alone or in combination with bacteriocins and/or antibodies. The invention is useful for treating a variety of inflammatory disorders including acne, psoriasis, eczema, atopic dermatitis and inflammatory bowel disease.

Abstract: Gram-negative bacterial mutants resistant to one or more stress conditions, including CO2, acid pH, and high osmolarity, and 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. Compositions are provided comprising one or more stress-resistant gram-negative bacterial mutants, preferably attenuated stress-resistant gram-negative bacterial mutants. Methods are provided for prophylaxis or treatment of a virally induced disease in a subject comprising administering to a subject a stress-resistant gram-negative bacterial mutants, preferably attenuated stress-resistant gram-negative bacterial mutants. The stress-resistant gram-negative bacterial mutants may serve as vectors for the delivery of one or more therapeutic molecules to a host.

Abstract: A genetically engineered live bacterium which is adapted to selectively replicate in and colonize a selected tissue type within the mammal, and concurrently produce within the selected tissue type at least one protease-sensitive cytotoxic molecule which is degradable by proteases within the selected tissue type, and at least one protease inhibitor peptide to inhibit the proteases within the selected tissue type from proteolytically degrading the protease sensitive cytotoxic molecule. The combination results in higher concentrations of the cytotoxic molecule local to the colonization, while permitting protease degradation of the cytotoxic molecule further away from the colonization.

Abstract: Bacterial strains are provided having at least one of a reduced size, a sialic acid coat, inducibly altered surface antigens, and expression of PD-L1 or CTLA-4 agonists and/or tryptophanase. The bacteria may have improved serum half-life, increased penetration into tumors, increased tumor targeting and increased antitumor activity. The bacteria are useful for delivery of therapeutic agents that treat of neoplastic diseases including solid tumors and lymphomas.

Abstract: Protease inhibitors together with protease sensitive therapeutics or diagnostics are provided, which may be ionically or covalently bound, or unbound. The protease inhibitors and/or protease sensitive moiety may be provided in monomeric, homopolymeric, heteropolymeric (for each of the protease and agent) and/or block copolymeric (combining polymers of agent and inhibitor) form. The inhibitors may be native active or e.g., protease activated. Multiple protease inhibitor peptides may be used in-frame with multiple protease cleavage signals (polymeric protease activated protease inhibitors). Combination with the protease inhibitors with the protease sensitive therapeutic enhances the intact, active molecule local-regional or targeted cell or tissue concentration, peak concentration and/or duration of the therapeutic exposure, thereby increasing its therapeutic efficacy. The protease inhibitors are particularly useful for tumor-targeted therapies and for vaccines.

Abstract: The present invention uses co-expression of protease inhibitors and protease sensitive therapeutic agents including phage and phagemids delivering peptides, therapeutic antibodies, DNA and RNA-based therapeutics that results in treating inflammation of a variety of disorders including psoriasis, atopic dermatitis and inflammatory bowel disease. The invention also provides bacteria that inhibit the growth of intestinal parasites such as worms, and deliver siRNA or miRNA that have specific anti-parasitic effects that results in the reduction or elimination of the parasite.

Abstract: Bacteria with tumor-targeting capability express, surface displayed, secreted and/or released modified chimeric therapeutic proteins with enhanced therapeutic activity against a neoplastic tissue including solid tumors, lymphomas and leukemias. The bacteria may be attenuated, non-pathogenic, low pathogenic or a probiotic. The chimeric proteins may be protease sensitive and may optionally be further accompanied by co-expression of a secreted protease inhibitor as a separate molecule or as a fusion.

Abstract: Chimeric proteins are expressed, secreted or released by a bacterium to immunize against or treat a parasite, infectious disease or malignancy. The delivery vector may also be attenuated, non-pathogenic, low pathogenic, or a probiotic bacterium. The chimeric proteins include chimeras of, e.g., phage coat and/or colicin proteins, bacterial toxins and/or enzymes, autotransporter peptides, lytic peptides, multimerization domains, and/or membrane transducing (ferry) peptides. The active portion of the immunogenic chimeric proteins can include antigens against a wide range of parasites and infectious agents, cancers, Alzheimer's and Huntington's diseases, and have enhanced activity when secreted or released by the bacteria, and/or have direct anti-parasite or infectious agent activity. The activity of the secreted proteins is further increased by co-expression of a protease inhibitor that prevents degradation of the effector peptides.

Abstract: Gram-negative bacterial mutants resistant stress conditions, including CO2, acid pH, and high osmolarity are provided, having reduced TNF-? induction having a msbB mutation, that are rendered stress-resistant by a mutation in the zwf gene. A method for prophylaxis or treatment of a virally induced disease in a subject comprising administering to said subject attenuated stress-resistant gram-negative bacterial mutants, is also provided, along with Methods for prophylaxis or treatment of a virally induced disease in a subject comprise administering to said subject one or more stress-resistant gram-negative bacterial mutants as vectors for the delivery of one or more therapeutic molecules. The methods provide efficient delivery of therapeutic molecules by stress-resistant gram-negative bacterial mutants engineered to express said therapeutic molecules.

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: A substantially purified substance having the properties of a bacterial microcin methionine analog, methionine synthesis inhibitor, tRNA-methionine synthase inhibitors or methionine competitive inhibitor capable of inhibiting tumor cell growth without inhibiting the growth of normal cells or treating neoplastic diseases, and may be used alone or in combination with other anti-cancer agents. The purified substance may also have anti-hyperhomocysteineuria and/or anti-infective properties, such as antifungal activity. The purified substance can be safely administered to animals including humans for the treatment of neoplastic, hyperhomocysteinemia and/or infectious diseases for the treatment of those diseases.

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.