The present invention features incapacitated whole-cell bacterial immunogenic compositions and methods of their production, which compositions are useful to deliver antigens in a manner resembling the live infectious organism in terms of elicitation of a robust immune response, but with reduced risk or no risk of disease. The compositions of the invention are produced by rendering a bacterium bacteriostatic through expression of a recombinant promoter in the bacterial cell, which promoter can be operably linked to a polynucleotide encoding a recombinant gene product. In one embodiment, where the bacterium is a gram negative host, the recombinant gene product provides for reduced toxicity of LPS. In one embodiment, the gene product is a bacteriophage protein, such as endolysin, holin, or ndd.

The present invention provides attenuated, aroA mutant B. bronchiseptica strains that are effective to elicit an immune response in an animal against B. bronchiseptica. Also provided are immunogenic compositions and vaccines which include the attenuated, aroA mutant B. bronchiseptica strains. Also provided are kits for use with such compositions and vaccines. Also provided are methods of orally administering attenuated, aroA mutant B. bronchiseptica strains, compositions, and vaccines to animals.

In one embodiment the invention provides a capsule for the oral administration of biopharmaceuticals to the gastrointestinal system. The capsule includes a capsule shell enveloping a lipophilic matrix permeated with discrete microcapsules. Each microcapsule is a hydrophilic matrix formed of an internal phase comprising an aqueous medium, stabilized into a discrete structure by a colloidal polymer, and containing the biopharmaceutical(s). The colloidal polymer typically is a hydrocolloid or an amphiphilic colloidal polymer.

Herein we describe construction of a select agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccine strain and demonstrate its ability to protect against acute respiratory glanders. Particularly, CLH001 is shown to be attenuated, safe, and effective at protecting against lethal B. mallei challenge. This strain should be useful in vaccines are for use in humans and animals, e.g., equines, in treating or providing immunoprotection against infections elicited by category B, tier 1 pathogens, in particular Burkholderia mallei (Bm) and B. pseudomallei, the causative agents of human glanders and melioidosis, respectively.

In certain embodiments, a recombinant attenuated derivative of a pathogenic Salmonella enterica serovar typhi cell is provided, (a) wherein one or more genes encoding subunits of a stg operon (Salmonella typhi Δstg) are inactivated or deleted resulting in a decrease of Stg adhesin/fimbriae production as compared to genes encoding a wild-type Stg operon (stgABCC′D), and/or (b) the cell comprises a nucleic acid encoding at least one of a gene encoding a subunit of a long polar fimbriae (Lpf) of S. enterica serovar Typhimurium protein. In certain embodiments, vaccines and compositions, and methods of use of the recombinant attenuated derivative of a pathogenic Salmonella enterica serovar typhi cell are provided.

The present invention provides a particle comprising a fusion protein, wherein the fusion protein comprises at least one NANP repeat (SEQ ID NO: 7), some or all of the C-terminus of the CS protein from Plasmodium falciparum and a hepatitis B surface antigen, and wherein the particle comprises no, or substantially no, free hepatitis B surface antigen protein, and uses thereof.

Provided are attenuated strains of M. tuberculosis and M. bovis BCG which are double auxotrophic mutants with genes knocked out in the biosynthetic pathways for arginine and methionine, and compositions and methods of use thereof.

Provided herein are compositions comprising substantially non-viable Gram-negative bacterial organisms that have a substantial reduction in endotoxin activity and/or pyrogenicity and methods for treating a cancer using the same. Also provided are methods for treating cancer provided herein, comprising administering to a mammal diagnosed with cancer, substantially non-viable Gram-negative bacteria having a substantial reduction in endotoxin activity and/or pyrogenicity, in an amount sufficient to inhibit growth or metastasis of the cancer. An additional method is provided comprising administering viable or non-viable Gram-negative bacterial organisms that have a genetic defect that results in a substantial loss of lipopolysaccharide within the outer membrane of the bacteria. Further provided are methods for reducing endotoxin activity and/or pyrogenicity in Gram-negative bacteria comprising treatment with polymyxin and glutaraldehyde.

A method of reducing or preventing the development of airway inflammation in a subject includes the step of infecting the respiratory tract of a subject an amount of a composition including a pharmaceutically acceptable carrier and live attenuated pertactin-deficient Bordetella bacteria sufficient to colonize the respiratory tract of the subject. The step of infecting the subject with the live attenuated pertactin-deficient Bordetella bacteria results in reduction or prevention of the development of airway inflammation in the subject.

The invention provides in part methods of treating cancers of a specific organ or tissue by administering a composition that is antigenically specific for one or more microbes that are pathogenic in the specific organ or tissue in which the cancer is situated.