Regulated expression of antigen and/or regulated attentuation to enhance vaccine immunogenicity and/or safety
AssigneesWashington University, Arizona Board of Regents for and on behalf of Arizona State University
InventorsRoy Curtiss III, Shifeng Wang, Soo-Young Wanda, Wei Kong
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Abstract
The invention relates to compositions and methods for making and using recombinant bacteria that are capable of regulated attenuation and/or regulated expression of one or more antigens of interest.
Claims17
A recombinant bacterium capable of the regulated expression of at least one nucleic acid sequence encoding an antigen of interest, and capable of regulated attenuation, wherein the bacterium comprises:
- (a) at least one chromosomally integrated nucleic acid sequence encoding a repressor operably linked to a regulatable promoter selected from the group consisting of PrhaBAD, PxylAB, and PxylFGH;
- (b) a vector comprising a nucleic acid sequence encoding at least one antigen of interest operably linked to a promoter regulated by the repressor, such that the expression of the nucleic acid sequence encoding the antigen is repressed during in vitro growth of the bacterium, but the bacterium is capable of high level expression of the nucleic acid sequence encoding the antigen in a host;
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- (c) a regulatable promoter chromosomally integrated so as to replace the native promoter of, and be operably linked to, at least one nucleic acid sequence of an attenuation protein.
A recombinant bacterium capable of regulated expression of at least one nucleic acid sequence encoding an antigen of interest, wherein the bacterium comprises
- a. at least one chromosomally integrated nucleic acid sequence encoding a repressor operably linked to a regulatable promoter, wherein the nucleic acid sequence encoding the repressor and/or promoter have been modified from the wild-type nucleic acid sequence so as to optimize the expression level of the nucleic acid sequence encoding the repressor, and
- b. a vector comprising at least one nucleic acid sequence encoding an antigen of interest operably linked to a promoter regulated by the repressor, such that the expression of the nucleic acid sequence encoding the antigen is repressed during in vitro growth of the bacterium, but the bacterium is capable of high level expression of the nucleic acid sequence encoding the antigen in a host.
Dependencies are inferred from the claim text.