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.
Claims29
A method for producing a carrier bacterium for delivery of a desired gene product to a host, comprising the steps of:
- (a) converting a rpoS-bacterium to a rpoS+ bacterium by introducing a recombiumt rpoS+ gene;
- (b) introducing one or more inactivating mutations which render said carrier bacterium attenuated;
- and
- (c) introducing a second recombinant gene encoding the desired gene product to a bacterium, wherein steps (a), (b), or (c) may be performed in any order.
A method for delivery of a desired gene product to a host with a carrier bacterium, the method comprising:
- (a) converting a rpoS− bacterium to a rpoS+ bacterium by introducing a recombinant rpoS+ gene;
- (b) introducing one or more inactivating mutations in a bacterium which render the bacterium attenuated;
- (c) introducing a second recombinant gene encoding the desired gene product to a bacterium, wherein steps (a), (b), or (c) may be performed in any order to yield said carrier bacterium;
- and
- (d) administering to the host said carrier bacterium.
A method for delivery of a desired gene product to a host, said method comprising
- (a) selecting for a strain of bacteria having (i) an RpoS+ phenotype, (ii) one or more inactivating mutations which render the strain attenuated, and (iii) a recombinant gene encoding the desired gene product;
- and
- (b) administering the strain to the host.
A method for producing from a parent bacteria strain, a carrier bacteria for the delivery of a desired gene product to a host, said method comprising generating a strain of bacteria having (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 method for producing a carrier bacteria for delivery of a desired gene product to a host, said method comprising selecting for a strain of bacteria having
- (a) an RpoS+ phenotype;
- (b) one or more inactivating mutations which render the strain attenuated;
- and
- (c) a recombinant gene encoding the desired gene product.
Dependencies are inferred from the claim text.