Induction of protective immunity against antigens
AssigneeUniversity of Florida Research Foundation, Inc.
InventorsRoy Curtiss, III, Shifeng Wang
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Abstract
Described herein are compositions and methods for making and using recombinant bacteria that are capable of regulated attenuation and/or regulated expression of one or more antigens from Clostridium Perfringens as vaccines to prevent necrotic enteritis (NE).
Claims41
A recombinant bacterium comprising a nucleic acid comprising:
- a sequence encoding a choloylglycine hydrolase (Cbh) antigen, or fragment thereof, or a sequence encoding a Clostridium perfringens enterotoxin (CpeC) antigen, or fragment thereof.
The recombinant bacterium of any one of the previous claims, wherein the Cbh antigen, or fragment thereof, is a fusion protein, and/or wherein the CpeC antigen, or fragment thereof, is a fusion protein.
The recombinant bacterium of any one of the previous claims, wherein the Cbh antigen, or fragment thereof, comprises a signal sequence, and/or wherein the CpeC antigen, or fragment thereof, comprises a signal sequence.
The recombinant bacterium of any one of the previous claims,
- wherein the sequence encoding the Cbh antigen is codon-optimized for expression in the bacterium, and/or
- wherein the sequence encoding the CpeC antigen is codon-optimized for expression in the bacterium.
The recombinant bacterium of any one of the previous claims, wherein the CpeC antigen is encoded by a epeC-max sequence.
The recombinant bacterium of any one of the previous claims, further comprising a sequence encoding a C-terminal domain of C. perfringens alpha toxin (PlcC) antigen, or fragment thereof.
The recombinant bacterium of any one of the previous claims, further comprising a sequence encoding a non-toxic necrotic enteritis B-like toxin (NetB) antigen, or fragment thereof.
The recombinant bacterium of any one of the previous claims, further comprising a sequence encoding a Fba antigen, or a fragment thereof.
The recombinant bacterium of claim 24, wherein the sequence encoding the Fba antigen, or fragment thereof, is codon optimized for expression in the bacterium.
The recombinant bacterium of any one of the previous claims, wherein the nucleic acid is present in a plasmid in the bacterium, or in the chromosome of the bacterium.
The bacterium of any one of the previous claims, further comprising a deletion in gene encoding an aspartate-semialdehyde dehydrogenase.
The bacterium of any one of the previous claims, further comprising a deletion in a sifA gene.
The bacterium of any one of the previous claims, comprising a balanced-lethal vector-host system.
The bacterium of any one of the previous claims, wherein the bacterium is a Gram-negative bacterium.
The bacterium of any one of the previous claims, wherein the bacterium belongs to the family Enterobacteriaceae.
The bacterium of any one of the previous claims, wherein the bacterium is of the genus Salmonella.
The bacterium of any one of the previous claims, wherein the bacterium is a Salmonella enterica bacterium.
The bacterium of any one of the previous claims, wherein the bacterium is a Salmonella enterica subsp. enterica serovar Paratyphi A bacterium, a Salmonella enterica subsp. enterica serovar Enteritidis bacterium, a Salmonella enterica subsp. enterica serovar Typhi bacterium, a Salmonella enterica subsp. enterica serovar Typhimurium bacterium, Salmonella enterica subsp. enterica serovar Dublin, Salmonella Pullorum, Salmonella Gallinarum, or Salmonella enterica subsp. enterica serovar Choleraesuis.
The bacterium of any one of the previous claims, wherein the bacterium is an attenuated derivative of a pathogenic bacterium.
A pharmaceutical composition comprising the recombinant bacterium of any one of the previous claims, and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.