Recombinant avirulent immunogenic S typhi having rpos positive phenotype
AssigneeWashington University
InventorsRoy Curtiss, III, Cheryl A. Nickerson
Life of this patent
Estimating the term…
Abstract
Avirulent immunogenic Salmonella enterica serotype Typhi and methods therefor are disclosed. The Salmonella have an RpoS.sup.+ phenotype, an inactivating mutation in one or more genes which renders the microbe avirulent, and a recombinant gene capable of expressing a desired protein. The Salmonella are avirulent and have high immunogenicity so that they can be used in vaccines and as delivery vehicles for the desired antigen. Also disclosed are methods for preparing the Salmonella and vaccine delivery vehicles therefor.
Claims41
A method for delivery of a desired gene product to a human comprising:
- (a) selecting for a strain of S. typhi having (i) as RpoS.sup.+ phenotype, (ii) one or more inactivating mutations which render the strain avirulent, and (iii) a recombinant gene encoding the desired gene product;
- and
- (b) administering the strain to the human.
A method for delivery of a desired gene product to a human comprising administering to the human a live avirulent strain of S. typhi having (a) a recombinant rpoS.sup.+ gene, (b) one or more inactivating mutations which render said microbe avirulent and (c) a second recombinant gene encoding the desired gene product.
A method for delivery of a desired gene product to a human comprising introducing a recombinant rpoS.sup.+ gene into a strain of S. typhi to produce a recombinant strain and administering the recombinant strain to the human wherein the recombinant strain administered to the human has (a) the recombinant rpoS.sup.+ gene, (b) an inactivating mutation in one or more genes which renders said microbe avirulent and (c) a second recombinant gene which encodes the desired product.
A method for producing a strain of carrier microbes for delivery of a desired gene product to a human comprising in any order the steps of:
- (a) selecting for a strain of S. typhi having an RpoS.sup.+ phenotype wherein said selecting comprises testing the strain for RpoS phenotype;
- (b) producing one or more inactivating mutations which render the strain avirulent;
- and
- (c) introducing into the strain a recombinant gene encoding a desired gene product.
A method for producing carrier microbes for delivery of a desired gene product to a human comprising generating a derivative of a Ty2 strain of S. typhi having (a) a recombinant rpoS.sup.+ gene, (b) one or more inactivating mutations which render said microbe avirulent and (c) a second recombinant gene encoding the desired gene product.
A method for producing a strain of cairier microbes for delivery of a desired gene product to a human comprising generating a recombinant strain of S. typhi having (a) a recombinant rpoS.sup.+ gene, (b) an inactivating mutation in one or more genes which renders the microbe avirulent and (c) a second recombinant gene which encodes the desired product, wherein said generating the recombinant strain of S. typhi comprises introducing a recombinant rpoS.sup.+ gene into a strain of S. typhi.
A carrier microbe for the delivery of a desired gene product to a human comprising a live avirulent derivative of a Ty2 S. typhi having (a) a recombinant rpoS.sup.+ gene, (b) one or more inactivating mutations which render said microbe avirulent and (c) a second recombinant gene encoding the desired gene product.
An immunogenic composition for use in a human comprising a live avirulent derivative of a Ty2 strain of S. typhi having (a) a recombinant rpoS.sup.+ gene, (b) one or more inactivating mutations which render said microbe avirulent and (c) a second recombinant gene encoding a desired gene product.
A method for assessing the immunogenicity of a Salmonella comprising determining the RpoS phenotype of said Salmonella wherein the presence of an RpoS.sup.+ phenotype indicates increased immunogenicity compared to an isogenic Salmonella having an RpoS.sup.- phenotype.
Dependencies are inferred from the claim text.