The present invention includes the discovery of a strain of Mycobacterium comprising an expression vector encoding a di-adenylate cyclase enzyme. The Mycobacterium is selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, or a combination thereof and the preferred strain of Mycobacterium is BCG. The preferred expression vector is a mycobacterial expression vector including an hsp60 promoter and a DNA sequence of diadenylate cyclase (disA), or a functional part thereof. The strains of Mycobacterium are used in therapeutic applications including tuberculosis and cancer.

The invention relates to the novel use of an immunogenic formulation containing the bacillus Calmette-Guérin (BCG) strain at a concentration between 104-109 bacteria, expressing at least one protein or immunogenic fragment of respiratory syncytial virus (RSV, Human orthopneumovirus), in a pharmaceutically acceptable saline buffer solution because it serves to prepare a vaccine useful to prevent, treat, or attenuate human metapneumovirus (hMPV) infections.

The present disclosure provides a method of treating a solid tumor cancer. The method includes administering a combination to a subject in need thereof. The combination includes at least two chemotherapy agents and a dose of a composition consisting essentially of attenuated Salmonella typhimurium. The present disclosure also provides an anti-tumor agent for use in a method of treating cancer. In such instances, the anti-tumor agent may include the combination.

Provided are modified bacteria and derivatives thereof that express antigens of interest. In some embodiments, the bacterium has a reduced genome and induces an enhanced immune response against the antigen of interest when administered to a subject as compared to an immune response that would have been induced by a bacterium of the same strain that has a full complement of genes. In some embodiments, the antigen is expressed on a surface of a bacterium. Also provided are method for producing antibody against antigens of interest, vaccine compositions, methods for vaccinating subjects, methods for treating cancers in subjects, methods for modulating inappropriate and undesirable immune response, methods for targeting materials in or on a human or animal that may be the cause of disease or otherwise undesirable phenotypes, and expression vectors for expressing antigens on the surface of reduced genome bacteria.

Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.

The present invention provides compositions or vaccines that contain a recombinant or an attenuated Leptospira interrogans that elicit an immune response in animals against Leptospira infection, including compositions comprising said recombinant or attenuated L. interrogans, methods of vaccination against Leptospira, and kits for use with such methods and compositions.

Provided herein are genetically engineered Vibrio cholerae bacterial strains, compositions including the bacterial strains, and methods of using the same for the prevention of Vibrio cholerae infection in a subject.

Helicobacter pylori is a leading cause of gastric mucosal inflammation, peptic ulcers, and gastric adenocarcinoma. Emerging antimicrobial-resistant H. pylori has hampered the successful eradication of frequent chronic infections. Additionally, due to the absence of effective vaccines against H. pylori, a safe vaccine is highly demanded. Disclosed herein are innovative Protective Immunity Enhanced Salmonella Vaccine (PIESV) vector strains to deliver and express multiple H. pylori antigen genes Immunization of mice with a vaccine delivering the HpaA, NapA (also termed Hp-NAP), UreA and UreB antigens, provided sterile protection against H. pylori SS1 infection in 7 out of 10 tested mice. Compared to the control groups that had received PBS or a PIESV with an empty vector, immunized mice exhibited specific and significant cellular recall responses and antigen-specific IgG2c, IgG1, total IgG and gastric IgA antibody titers. Importantly, the mice immunized with the vaccine candidate showed a significant reduction in a load of an unidentified Gram-positive rod-shaped bacteria in their stomach compared to the control groups. In conclusion, a Salmonella Typhimurium-based live vaccine delivering four antigens shows promise as a safe and effective vaccine against H. pylori infection.

The invention relates to modified Mycobacterium cells, and their uses as vaccines, and, particularly, modified Bacillus Calmette-Guérin vaccines. The invention extends to the use of the modified vaccines for vaccination applications in a wide range of animals, including cattle and humans. The invention extends to novel antigens, kits and compositions comprising these novel antigens and to their use in diagnosis. The invention also extends to apparatus comprising the modified vaccine and the antigens, and compositions comprising the antigens.

The present invention discloses a vaccine formulation in accordance with an illustrative embodiment. The formulation including a live attenuated cholera vaccine strain VCUSM14P; a vaccine medium having starch, cellulose, dextrose, and yeast extract; and a phosphate buffer saline.