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US 9,481,888 B2Granted
Recombinant bacterium and methods of antigen and nucleic acid delivery
AssigneeArizona Board of Regents for and on behalf of Arizona State University
InventorsRoy Curtiss, III, Wei Kong
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Abstract
The present invention provides a recombinant bacterium and methods of using the recombinant bacterium to induce an immune response.
Claims21
A recombinant Salmonella bacterium, wherein the bacterium comprises:
- (a) a mutation selected from the group consisting of a ΔPhilA::PtrcΔlacO hilA mutation and a ΔPhilA::PhilA hilA mutation, wherein the ΔPhilA::PhilA hilA mutation comprises a mutation in the hilA promoter that reduces nucleoid-associated protein H-NS binding,
- (b) a ΔtlpA mutation and a ΔsseL mutation and, optionally at least one mutation selected from the group consisting of an ampG mutation, an ampD mutation, and a nagE mutation, and
- (c) at least one mutation selected from the group consisting of a tlyC mutation, a pld mutation, a ΔsifA mutation and a ΔPsifA::TT araC PBAD sifA mutation.
A recombinant Salmonella bacterium, wherein the bacterium is:
- (a) capable of regulated delayed attenuation,
- (b) capable of regulated delayed lysis, characterized by a ΔPmurA::TT araC PBAD murA mutation and a ΔasdA::TT araC PBAD c2 mutation,
- (c) capable of escape from a host endosomal compartment, characterized by at least one mutation selected from the group consisting of a tlyC mutation and a pld mutation,
- (d) capable of hyper-invasion, characterized by hilA operably linked to a constitutive promoter, and
- (e) capable of reducing bacterium-induced host programmed cell death, characterized by a ΔtlpA mutation and a ΔsseL mutation and, optionally, at least one mutation selected from the group consisting of an ampG mutation, an ampD mutation, and a nagE mutation.
2 more elements
A recombinant Salmonella bacterium, wherein the bacterium is:
- (a) capable of regulated delayed attenuation,
- (b) capable of regulated delayed lysis, characterized by ΔPmurA::TT araC PBAD murA mutation and a ΔasdA::TT araC PBAD c2 mutation,
- (c) capable of escape from a host endosomal compartment, characterized by at least one mutation selected from the group consisting of a tlyC mutation, a pld mutation, a ΔsifA mutation and ΔPsifA::TT araC PBAD sifA mutation,
- (d) capable of hyper-invasion, characterized by hilA operably linked to a constitutive promoter, and
- (e) capable of reducing bacterium-induced host programmed cell death, characterized by a ΔtlpA mutation and a ΔsseL mutation and, optionally, a mutation selected from the group consisting of an ampG mutation, an ampD mutation, and a nagE mutation.
2 more elements
A recombinant Salmonella bacterium, wherein the bacterium is:
- (a) capable of regulated delayed attenuation,
- (b) capable of regulated delayed lysis, characterized by a ΔPmurA::TT araC PBAD murA mutation and a ΔasdA::TT araC PBAD c2 mutation,
- (c) capable of escape from a host endosomal compartment, characterized by at least one mutation selected from the group consisting of a tlyC mutation, a pld mutation, a ΔsifA mutation and ΔPsifA::TT araC PBAD sifA mutation, and
- (d) capable of reducing bacterium-induced host programmed cell death, characterized by a ΔtlpA mutation and a ΔsseL mutation and, optionally, a mutation selected from the group consisting of an ampG mutation, an ampG mutation, and a nagE mutation.
1 more element
Dependencies are inferred from the claim text.