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AssigneeAviex Technologies LLC
InventorDavid Gordon Bermudes
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Gram-negative bacteria, and compositions containing the bacteria, resistant to one or more stress conditions, including, but not limited to, CO2, acid pH, and high osmolarity, having reduced TNF-αinduction having a mutation in one or more lipid biosynthesis genes, e.g., msbB, rendered stress-resistant by a mutation in the zwf gene are provided. Methods for prophylaxis or treatment of a virally induced disease in a subject comprising administering preferably attenuated stress-resistant gram-negative bacterial mutants. and for prophylaxis or treatment of a virally induced disease in a subject comprising administering one or more stress-resistant gram-negative bacterial mutants as vectors for the delivery of one or more therapeutic molecules are provided.
A live genetically engineered YS873 mutant Salmonella bacterium, comprising an antigen-expressing plasmid or chromosomally integrated cassette comprising at least one nucleic acid sequence that encodes and directs expression of a heterologous fusion peptide comprising a viral antigen region comprising one or more viral antigens and a bacterial protein secretion promoting region linked in-frame to the antigenic peptide, the at least one nucleic acid sequence being expressed as a heterologous fusion peptide which is compatible with a Salmonella peptide secretion system, the YS873 Salmonella mutant comprising a first attenuating to the msbB gene, a second loss of function mutation to the somA gene, and having a further loss of function mutation to the zwf gene.
A live genetically engineered YS873 mutant Salmonella bacterium, adapted for therapeutic administration to an animal, comprising an antigen-expressing plasmid or chromosomally integrated cassette comprising at least one nucleic acid sequence that encodes and directs expression of a heterologous fusion peptide comprising a viral antigen region comprising a viral antigen and a bacterial protein secretion promoting region linked in-frame to the antigenic peptide, the at least one nucleic acid sequence being expressed as a heterologous fusion peptide which is compatible with a Salmonella peptide secretion system, the secreted heterologous fusion protein being adapted to stimulate the host immune response to the antigenic polypeptide, the YS873 Salmonella mutant comprising a first attenuating mutation to the msbB gene, a second loss of function mutation to the somA gene, and having a further loss of function mutation to the zwf gene.
A live genetically engineered YS873 mutant Salmonella bacterium, adapted for treatment of an animal by oral administration, comprising an antigen-expressing plasmid or chromosomally integrated cassette comprising at least one nucleic acid sequence that encodes and directs expression of a heterologous fusion peptide comprising a viral antigen region and a bacterial protein secretion promoting region linked in-frame to the antigenic peptide, the at least one nucleic acid sequence being expressed as a heterologous fusion peptide which is compatible with a Salmonella peptide secretion system, the YS873 Salmonella mutant comprising a first attenuating mutation to the msbB gene, a second loss of function mutation to the somA gene, and having a further loss of function mutation to the zwf gene.
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