Mutated Salmonella enteriaca
Inventors
BEARSON, Bradley L. • BEARSON, Shawn M.
Assignees
US Department of Agriculture USDA
Publication Number
US-9868769-B2
Publication Date
2018-01-16
Expiration Date
2034-12-29
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Abstract
A novel, mutated Salmonella enterica serovar Typhimurium vaccine is generated and imparts protective immunity in vaccinated animals for a range of S. enterica serovars. The vaccine can be attenuated or inactivated, including bacterial ghosts or membrane fractions thereof. Immunogenic compositions are included in the invention and methods of generating an immune response.
Core Innovation
This invention relates to a novel, mutated Salmonella enterica serovar Typhimurium that generates an immune response in animals, particularly porcine and avian species, to reduce morbidity, mortality, transmission, colonization, and carriage caused by any serovar of Salmonella enterica. The mutated strains can be live attenuated, inactivated, bacterial ghosts, or membrane fractions and are formulated into immunogenic compositions to induce protective immunity across a range of Salmonella serovars.
The problem being addressed is the high prevalence and pathogenicity of Salmonella serovars in animals and humans, causing significant morbidity and mortality, particularly through foodborne infections linked to animal carriers that shed bacteria without overt illness. Existing vaccines are serovar-specific and provide limited cross-protection against diverse Salmonella serovars, leaving a gap for effective, broad immunogenic compositions. Prior approaches utilizing limited mutations have failed to confer long-term immunity or broad cross-serovar protection.
The invention solves these problems by creating mutated S. enterica serovar Typhimurium strains with null mutations in genes involved in lipopolysaccharide synthesis (such as rfaH) combined with null mutations in one or more small regulatory RNA genes (rybB, micA, omrA, omrB, and invR). These mutations reduce LPS synthesis and increase exposure of conserved outer membrane proteins, thus eliciting a stronger and cross-protective immune response. Specific strains, including BBS 866 and BBS 1134, exhibit attenuated phenotypes and provide protection upon vaccination, significantly reducing colonization, shedding, and systemic infection in animal models.
Claims Coverage
The claims focus on a mutated Salmonella enterica serovar Typhimurium vaccine strain and its immunogenic compositions, including methods of use and kits. There are multiple independent claims addressing the mutated strains, compositions, methods of inducing immune responses, reducing carriage and colonization, and the preparation of kits.
Mutations in Salmonella genes for broad immune protection
A mutated S. enterica serovar Typhimurium possessing null mutations in the invR, micA, rybB, rfaH, omrA, and omrB genes, providing broad cross-protection against multiple Salmonella serovars.
Immunogenic composition comprising mutated Salmonella strains
An immunogenic composition containing a pharmaceutically acceptable carrier or diluent and the mutated Salmonella strain with the specified null mutations, optionally including an adjuvant, wherein the mutated strain can be attenuated or inactivated (including as bacterial ghosts or membrane fractions).
Methods of immune response induction and carriage reduction by administration
Methods of inducing an immune response or reducing Salmonella carriage and colonization in animals by administering an immunologically effective amount of the immunogenic composition containing the mutated Salmonella strain with null mutations in invR, micA, rybB, rfaH, omrA, and omrB, optionally with an adjuvant.
Kits for vaccination against Salmonella
Kits comprising (1) a mutated Salmonella strain with null mutations in the specified genes, (2) a pharmaceutically acceptable carrier or diluent, (3) written instructions for use, and optionally (4) an adjuvant; wherein the mutated strain may be attenuated or inactivated, including strains BBS 866 and BBS 1134.
The claims collectively cover the mutated Salmonella strains with specific null mutations, immunogenic compositions comprising these strains in various forms, methods to induce protective immune responses and reduce Salmonella carriage in animals, and kits for administration, emphasizing broad cross-serovar protection and various administration formats.
Stated Advantages
The mutated strains provide a broad immune response against multiple Salmonella enterica serovars beyond serovar-specific vaccines.
The vaccine strains are attenuated, reducing morbidity and mortality in vaccinated animals.
They reduce Salmonella transmission, colonization, and fecal shedding in animals, improving food safety and public health.
The immunogenic compositions can be live attenuated, inactivated, bacterial ghosts, or membrane fractions, offering versatile vaccine formats.
The vaccine strain BBS 866 functions as a DIVA vaccine, allowing differentiation of infected from vaccinated animals without interfering with serological monitoring.
Documented Applications
Use as a vaccine to induce immune responses in porcine, turkeys, and other animals against various Salmonella enterica serovars including S. enterica serovar Typhimurium, Choleraesuis, and Heidelberg.
Reducing Salmonella carriage, colonization, and transmission in food-producing animals to improve animal health and reduce foodborne disease risks in humans.
Inducing cross-protective immunity in mammals and birds to prevent systemic infection and gastrointestinal colonization by Salmonella spp.
Formulation of immunogenic compositions including live attenuated or inactivated (including bacterial ghosts and membrane fractions) mutated Salmonella strains for administration via various routes including intranasal, oral, and injection.
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