Recombinant vaccines comprising immunogenic attenuated bacteria having RPOS positive phenotype
AssigneeWashington University
InventorsRoy Curtiss, III, Cheryl A. Nickerson
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Abstract
Attenuated immunogenic bacteria having an RpoS+ phenotype, in particular, Salmonella enterica serotype Typhi having an RpoS+ phenotype and methods therefor are disclosed. The Salmonella have in addition to an RpoS+ phenotype, an inactivating mutation in one or more genes which render the microbe attenuated, and a recombinant gene capable of expressing a desired protein. The Salmonella are attenuated and have high immunogenicity so that they can be used in vaccines and as delivery vehicles for genes and gene products. Also disclosed are methods for preparing the vaccine delivery vehicles.
Claims31
A method for producing, from a parent bacteria strain, a carrier bacteria for the delivery of a desired gene product to a human comprising generating a strain of bacteria comprsising (a) a recombinant rpoS+ gene;
- (b) one or more inactivating mutations which render said bacteria attenuated;
- and (c) a second recombinant gene encoding the desired gene product, wherein said carrier bacteria expresses a higher level of RpoS gene product than said parent bacteria strain and wherein said higher level of RpoS gene product confers upon the carrier bacteria high immunogenicity relative to said parent bacteria strain.
A genetically engineered bacterial cell, wherein said genetically engineered bacterial cell (a) is produced from a parent bacterial cell, (b) is a live attenuated strain of bacteria, (c) has a recombinant rpoS+ gene, (d) has one or more inactivating mutations which render said bacteria attenuated and (e) has a second recombinant gene encoding a desired gene product, and wherein the genetically engineered bacterial cell expresses a higher level of RpoS gene product than said parent bacteria cell and wherein said higher level of RpoS gene product confers upon the genetically engineered bacterial cell high immunogenicity relative to said parent bacteria strain.
Dependencies are inferred from the claim text.