The present disclosure provides uses of genetically engineered attenuated Salmonella typhimurium strain VNP20009-M in preventing and treating cancer metastasis. The genetically engineered strain VNP20009-M is targeted to cancer cells and has a significant effect of inhibiting metastasis and growth. VNP20009-M can be used to prepare medicaments for the prevention and treatment of tumor metastasis.

The present invention relates to a method of preparing a live attenuated vaccine by irradiation and a live attenuated vaccine composition prepared by the same, and more particularly, a method of preparing a live attenuated vaccine by irradiation including irradiating a pathogenic microorganism with a dose of 0.5 to 2 kGy of radiation per single radiation six to fifteen times; and a live attenuated vaccine composition including a pathogenic microorganism attenuated to not be revertant to a wild type by generation of at least one mutation of nucleotide insertion and nucleotide deletion by irradiation.

The present disclosure relates to Salmonella Gallinarum mutant strains and uses thereof. A vaccine composition according to an aspect has no risk of recovering pathogenicity, has no residual pathogenicity due to detoxification of an endotoxin, and does not cause lesions and bacterial re-isolation, thereby exhibiting significantly improved safety compared to the existing fowl typhoid vaccines. In addition, since the vaccine composition induces a high-level immune response even when administered to young chicks, it may be used regardless of age, and as the vaccine strain may be used as a live vaccine having an excellent protective capability by itself, the vaccine composition may be useful for preventing and alleviating fowl typhoid.

Provided are bacterial strains, methods of culturing bacterial cells using synthetic quorum-regulated lysis, and uses thereof.

Bacterial strains are provided having at least one enhanced mechanism to sequester, bind, precipitate, chemically oxidize or reduce copper ions or other toxic divalent transition metals. The bacteria may also have optional copper resistance mechanisms. The bacteria reduce the amount of available copper to tissues, which may be cancerous tissues, and reduce tumor growth, angiogenesis and/or metastasis, or tissues subject to excess copper due to host defects in copper metabolism. The bacteria are useful for treatment of neoplastic diseases including solid tumors and lymphomas, as well as Wilson's Disease, Menke's Disease, and possible Alzheimer's Disease, Parkinson's Disease, and Creutzfeldt-Jakob Disease.

Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and/or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella, or by modification of the genes so that functional flagella are not produced, and/or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellin.sup.− and/or pagP.sup.−. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine or purine auxotrophs. The bacteria optionally are one or more of asd.sup.−, purI.sup.−, and msbB.sup.−. The immunostimulatory bacteria, such as Salmonella species, are modified to encode immunostimulatory proteins that confer anti-tumor activity in the tumor microenvironment, and/or are modified so that the bacteria preferentially infect immune cells in the tumor microenvironment, or tumor-resident immune cells, and/or are modified to induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

A generic inert bio-vector Salmonella sp. S9H and potential uses thereof are provided. The generic inert bio-vector Salmonella sp. S9H is derived from a continuous in-vitro culture of an inert bio-vector bacterium Salmonella sp. S9 by using LB solid and liquid culture media for passage to the fortieth generation. With a quantity of bacteria at a working concentration, the S9H does not cause non-specific agglutination reactions in sera or whole blood derived from humans, mice, cattle, pigs and poultry (including chickens, ducks, geese, turkeys, pigeons and quails); moreover, S9H has a property of carrying, and expressing and displaying different antigen factors derived from humans, mice, cattle, pigs and poultry (including chickens, ducks, geese, turkeys, pigeons and quails) on the surface thereof .

Provided are attenuated immunostimulatory bacteria with genomes that are modified to, for example, reduce toxicity and improve the anti-tumor activity, such as by increasing accumulation in the tumor microenvironment, particularly in tumor-resident myeloid cells, improving resistance to complement inactivation, reducing immune cell death, promoting adaptive immunity, and enhancing T-cell function. The increase in colonization of phagocytic cells improves the delivery of encoded therapeutic products to the tumor microenvironment and tumors, and permits, among other routes, systemic administration of the immunostimulatory bacteria.

Disclosed herein are unique adjuvant compositions comprising an attenuated derivative of a self-destructing bacterial pathogen that undergoes lysis in vivo. In exemplary embodiments, the bacterial pathogen is a Salmonella spp. Also disclosed are methods for enhancing an immune response using the adjuvants disclosed herein.

The invention provides isolated achromosomal dynamic active systems (ADAS), including highly active ADAS. These ADAS provided by the invention can be obtained by a variety of means. Various associated methods of making and using these ADAS are provided.