Mutated Salmonella enterica
Inventors
BEARSON, Bradley L. • BEARSON, Shawn M.
Assignees
US Department of Agriculture USDA
Publication Number
US-10351606-B2
Publication Date
2019-07-16
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 can be used to generate an immune response in animals such as porcine and avian species. The immune response helps reduce morbidity and mortality caused by any serovar of Salmonella enterica and decreases transmission, colonization, and carriage of any serovar in the animal.
The invention provides mutated strains of S. enterica serovar Typhimurium containing one or more mutations in genes involved in lipopolysaccharide (LPS) synthesis and in regulatory small RNA (sRNA) genes including rfaH, omrA, omrB, rybB, micA, and invR. These mutated bacteria can be live attenuated, inactivated, bacterial ghosts, or membrane fractions, and induce cross-protective immunity against various Salmonella serovars in animals.
The problem addressed is the widespread prevalence and pathogenicity of Salmonella species causing significant disease in humans and animals, exacerbated by large-scale animal husbandry environments. Existing vaccines tend to be serovar-specific and do not confer broad protection or long-term immunity. Prior approaches to attenuating Salmonella involved limited mutations that failed to provide comprehensive cross-protection or durable immunity.
Claims Coverage
The patent includes one independent claim focused on a method of generating an immune response in animals against Salmonella enterica using a specific mutated bacterial composition. The main inventive features involve the composition details and the induced immune response.
Use of mutated Salmonella enterica serovar Typhimurium with defined null mutations
Administration of an immunogenic composition comprising a mutated S. enterica serovar Typhimurium with null mutations in invR, micA, rybB, rfaH, omrA, and omrB genes to generate an immune response in animals.
Inclusion of adjuvant in immunogenic composition
The immunogenic composition can further comprise an adjuvant to enhance the immune response.
Attenuated or inactivated mutant bacteria
The mutated S. enterica serovar Typhimurium used in the immunogenic composition can be attenuated or inactivated, including as bacterial ghosts.
Use of specific bacterial strains
The mutated strains specifically include S. enterica serovar Typhimurium strains BBS 866 and BBS 1134, deposited under accession numbers NRRL B-50989 and NRRL B-50990, respectively.
Cross-reactive immune response
The immune response generated is cross-reactive against various S. enterica serovars including Typhimurium, Choleraesuis, Heidelberg, Dublin, Abortus-equi, Abortus-ovi, Enteritidis, Arizonae, and Gallinarum.
Humoral and cellular immune responses
The generated immune response can be humoral, cellular, or both to provide protection against Salmonella infections.
The claims cover a method of inducing broad and cross-protective immune responses in animals by administering immunogenic compositions containing mutated Salmonella enterica serovar Typhimurium with specific null mutations, optionally including adjuvants and using defined bacterial strains, capable of eliciting both humoral and cellular immunity.
Stated Advantages
The mutated Salmonella enterica serovar Typhimurium strains provide broad cross-protection against multiple Salmonella serovars beyond serovar-specific vaccines.
The mutations, including in LPS synthesis and sRNA genes, result in attenuated bacteria suitable for live vaccination with reduced pathogenicity.
The vaccine strains reduce colonization, carriage, transmission, and fecal shedding of Salmonella, thereby improving food safety and animal health.
The vaccine can be formulated as live attenuated, inactivated, bacterial ghosts, or membrane fractions, providing flexibility in vaccine formulation.
The strains act as DIVA vaccines allowing differentiation of infected from vaccinated animals without interfering with serological monitoring programs.
Documented Applications
Generating broad immune responses in animals such as swine, turkeys, and other avian species to protect against Salmonella enterica infections.
Preventing or treating diseases caused by diverse Salmonella serovars in food-producing and other animals to reduce morbidity and mortality.
Reducing gastrointestinal colonization, pathogen fecal shedding, and transmission of Salmonella enterica in livestock and poultry, thereby enhancing public health and food safety.
Use as vaccines administered via various routes including intranasal, oral, or injection for prophylactic or therapeutic immunization.
Use as bacterial ghosts or membrane protein fractions for vaccine formulations.
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