Abstract: The present invention provides compositions and methods for inducing an immune response in a subject in need thereof, comprising administering to the subject an immunologically-effective amount of a live Salmonella Typhi vector, wherein the Salmonella Typhi vector has been engineered to express one or more cancer antigens. In some aspects the vector has been engineered to express an outer membrane folding protein BamA or a fragment or variant thereof; and a lipid A deacylase PagL or a fragment or variant thereof, wherein the Salmonella Typhi vector is capable of delivering the antigen to a mucosal tissue or subcutaneously to dendritic cells via an outer membrane vesicle when administered to a subject.

Abstract: The present invention provides compositions and methods of inducing an immune response in a subject in need thereof, comprising administering to the subject an immunologically-effective amount of a live Salmonella Typhi vector comprising a heterologous antigen from a pathogen, wherein the heterologous antigen comprises an outer membrane protein, an antigenic fragment thereof or a variant thereof, wherein the antigen is delivered to a mucosal tissue of the subject by an outer membrane vesicle.

Abstract: The present invention provides compositions and methods of inducing an immune response in a subject in need thereof, comprising administering to the subject an immunologically-effective amount of a live Salmonella typhi vector, wherein the Salmonella typhi vector has been engineered to express one or more antigens; an outer membrane folding protein Barn A or a fragment or variant thereof; and a lipid A deacylase PagL or a fragment or variant thereof, wherein the Salmonella typhi vector is capable of delivering the antigen to a mucosal tissue via an outer membrane vesicle when administered to a subject.

Abstract: The present invention provides compositions and methods of inducing an immune response in a subject in need thereof, comprising administering to the subject an immunologically-effective amount of a live Salmonella Typhi vector comprising a heterologous antigen from a pathogen, wherein the heterologous antigen comprises an outer membrane protein, an antigenic fragment thereof or a variant thereof, wherein the antigen is delivered to a mucosal tissue of the subject by an outer membrane vesicle.

Abstract: The invention relates to a multivalent Clostridium difficile vaccine comprising a Salmonella Typhi live vector comprising the cell binding domain of TcdA toxin (CBD/A) of Clostridium difficile or an antigenic fragment thereof and the cell binding domain of TcdB toxin (CBD/B) of Clostridium difficile or an antigenic fragment thereof and optionally the cell-binding subunit component (CdtB) of binary toxin of Clostridium difficile or an antigenic fragment thereof. The invention further provides methods of inducing an immune response and methods of preventing recurrence of C. difficile infections in subjects.

Abstract: Bacterial live vector vaccines represent a vaccine development strategy that offers exceptional flexibility. In the present invention, genes encoding protective antigens of unrelated bacterial, viral, parasitic, or fungal pathogens are expressed in an attenuated bacterial vaccine strain that delivers these foreign antigens to the immune system, thereby eliciting relevant immune responses. Rather than expressing these antigens using only low copy expression plasmids, expression of foreign proteins is accomplished using both low copy expression plasmids in conjunction with chromosomal integrations within the same live vector. This strategy compensates for the inherent disadvantage of loss of gene dosage (versus exclusive plasmid-based expression) by integrating antigen expression cassettes into multiple chromosomal sites already inactivated in an attenuated vector.

Abstract: Bacterial live vector vaccines represent a vaccine development strategy that offers exceptional flexibility. In the present invention, genes encoding protective antigens of unrelated bacterial, viral, parasitic, or fungal pathogens are expressed in an attenuated bacterial vaccine strain that delivers these foreign antigens to the immune system, thereby eliciting relevant immune responses. Rather than expressing these antigens using only low copy expression plasmids, expression of foreign proteins is accomplished using both low copy expression plasmids in conjunction with chromosomal integrations within the same live vector. This strategy compensates for the inherent disadvantage of loss of gene dosage (versus exclusive plasmid-based expression) by integrating antigen expression cassettes into multiple chromosomal sites already inactivated in an attenuated vector.

Abstract: Bacterial live vector vaccines represent a vaccine development strategy that offers exceptional flexibility. In the present invention, genes encoding protective antigens of unrelated bacterial, viral, parasitic, or fungal pathogens are expressed in an attenuated bacterial vaccine strain that delivers these foreign antigens to the immune system, thereby eliciting relevant immune responses. Rather than expressing these antigens using only low copy expression plasmids, expression of foreign proteins is accomplished using both low copy expression plasmids in conjunction with chromosomal integrations within the same live vector. This strategy compensates for the inherent disadvantage of loss of gene dosage (versus exclusive plasmid-based expression) by integrating antigen expression cassettes into multiple chromosomal sites already inactivated in an attenuated vector.

Abstract: Bacterial live vector vaccines represent a vaccine development strategy that offers exceptional flexibility. In the present invention, genes encoding protective antigens of unrelated bacterial, viral, parasitic, or fungal pathogens are expressed in an attenuated bacterial vaccine strain that delivers these foreign antigens to the immune system, thereby eliciting relevant immune responses. Rather than expressing these antigens using only low copy expression plasmids, expression of foreign proteins is accomplished using both low copy expression plasmids in conjunction with chromosomal integrations within the same live vector. This strategy compensates for the inherent disadvantage of loss of gene dosage (versus exclusive plasmid-based expression) by integrating antigen expression cassettes into multiple chromosomal sites already inactivated in an attenuated vector.

Abstract: The disclosure below provides a protein export system utilizing non-hemolytic variants of HlyE family member proteins for efficiently producing recombinant protein from a host cell. In a preferred embodiment, the protein export system utilizes protein export machinery endogenous to the host bacterium into which the protein export system vector is introduced.

Abstract: The present invention is drawn to multivalent Salmonella enterica serovar conjugate vaccines comprising conjugates of S. Typhimurium, S. Enteritidis, S. Choleraesuis, S. Typhi, S. Paratyphi A and optionally S. Paratyphi B, wherein the conjugates comprise a hapten antigen and a carrier antigen, wherein at least one of the hapten antigens or carrier antigens is characteristic of the Salmonella enterica serovar. The present invention also provides Salmonella enterica serovar reagent strains to produce the multivalent conjugate vaccines and attenuated Salmonella enterica serovars for use as vaccines.

Abstract: The present invention relates generally to stabilized expression plasmid systems. The stabilized expression plasmid systems comprise an expression vector that includes a plasmid maintenance system (PMS) and, optionally, one or both of a polynucleotide encoding a selected antigen under control of a promoter, and a polynucleotide encoding a selectable marker under control of a promoter. The use of the mchI protein as a selectable marker is found in preferred embodiments of the invention.

Abstract: The invention relates to a multivalent Clostridium difficile vaccine comprising a Salmonella Typhi live vector comprising the cell binding domain of TcdA toxin (CBD/A) of Clostridium difficile or an antigenic fragment thereof and the cell binding domain of TcdB toxin (CBD/B) of Clostridium difficile or an antigenic fragment thereof and optionally the cell-binding subunit component (CdtB) of binary toxin of Clostridium difficile or an antigenic fragment thereof. The invention further provides methods of inducing an immune response and methods of preventing recurrence of C. difficile infections in subjects.

Abstract: The present invention relates generally to a Plasmid Maintenance System for the stabilization of expression plasmids encoding foreign antigens, and methods for making and using the Plasmid Maintenance System. The invention optimizes the maintenance of expression plasmids at two independent levels by: (1) removing sole dependence on balanced lethal maintenance functions; and (2) incorporating at least one plasmid partition function to prevent random segregation of expression plasmids, thereby enhancing their inheritance and stability. The Plasmid Maintenance System may be employed within a plasmid which has been recombinantly engineered to express a variety of expression products.

Abstract: The disclosure below provides a protein export system utilizing non-hemolytic variants of HlyE family member proteins for efficiently producing recombinant protein from a host cell. In a preferred embodiment, the protein export system utilizes protein export machinery endogenous to the host bacterium into which the protein export system vector is introduced.

Abstract: The present invention relates generally to stabilized expression plasmid systems. The stabilized expression plasmid systems comprise an expression vector that includes a plasmid maintenance system (PMS) and, optionally, one or both of a polynucleotide encoding a selected antigen under control of a promoter, and a polynucleotide encoding a selectable marker under control of a promoter. The use of the mchI protein as a selectable marker is found in preferred embodiments of the invention.

Abstract: The disclosure below provides a protein export system for efficiently producing recombinant protein from a host cell. In a preferred embodiment, the protein export system utilizes protein export machinery endogenous to the host bacterium into which the protein export system vector is introduced.

Abstract: The present invention relates generally to a Plasmid Maintenance System for the stabilization of expression plasmids encoding foreign antigens, and methods for making and using the Plasmid Maintenance System. The invention optimizes the maintenance of expression plasmids at two independent levels by: (1) removing sole dependence on balanced lethal maintenance functions; and (2) incorporating at least one plasmid partition function to prevent random segregation of expression plasmids, thereby enhancing their inheritance and stability. The Plasmid Maintenance System may be employed within a plasmid which has been recombinantly engineered to express a variety of expression products.

Abstract: The present invention relates generally to a Plasmid Maintenance System for the stabilization of expression plasmids encoding foreign antigens, and methods for making and using the Plasmid Maintenance System. The invention optimizes the maintenance of expression plasmids at two independent levels by: (1) removing sole dependence on balanced lethal maintenance functions; and (2) incorporating at least one plasmid partition function to prevent random segregation of expression plasmids, thereby enhancing their inheritance and stability. The Plasmid Maintenance System may be employed within a plasmid which has been recombinantly engineered to express a variety of expression products.

Abstract: The present invention relates generally to a Plasmid Maintenance System for the stabilization of expression plasmids encoding foreign antigens, and methods for making and using the Plasmid Maintenance System. The invention optimizes the maintenance of expression plasmids at two independent levels by: (1) removing sole dependence on balanced lethal maintenance functions; and (2) incorporating at least one plasmid partition function to prevent random segregation of expression plasmids, thereby enhancing their inheritance and stability. The Plasmid Maintenance System may be employed within a plasmid which has been recombinantly engineered to express a variety of expression products.