The present invention encompasses a recombinant Yersinia pestis bacterium and a vaccine comprising a recombinant Yersinia pestis bacterium.
1. A recombinant Yersinia pestis bacterium, wherein the bacterium comprises the plasmid pCD1, and comprises a araC P BAD crp mutation such that the bacterium has regulated delayed attenuation.
2. The recombinant Yersinia pestis bacterium of claim 1 , further comprising a regulated expression mutation.
3. A vaccine comprising a recombinant bacterium of claim 1 .
4. The vaccine of claim 3 , wherein the vaccine elicits a protective immune response against both pneumonic and bubonic plague.
5. The vaccine of claim 3 , wherein the vaccine elicits an immune response against Yersinia and at least one additional pathogen.
6. The recombinant Yersinia pestis bacterium of claim 1 , wherein the bacterium is infectious.
7. A recombinant Yersinia pestis bacterium, wherein the bacterium comprises:
a) pCD1,
b) a araC P BAD crp mutation such that the bacterium has regulated delayed attenuation
(c) a mutation in relA such that ppGpp synthesis is decreased, and
(d) a mutation in spoT such that ppGpp synthesis is decreased.
8. The recombinant bacterium of claim 7 , wherein the bacterium is infectious.
9. The recombinant bacterium of claim 1 , wherein the bacterium comprises:
a) pCD1,
b) a araC P BAD crp mutation such that the bacterium has regulated delayed attenuation,
(c) a mutation in relA such that ppGpp synthesis is decreased, and
(d) a mutation in spoT such that ppGpp synthesis is decreased.
10. The recombinant bacterium of claim 1 , wherein the bacterium comprises:
a) pCD1,
b) a araC P BAD crp mutation such that the bacterium has regulated delayed attenuation, and
c) a second regulated attenuation mutation, such that the bacterium is capable of colonizing a host in a non-attenuated manner, and ppGpp synthesis is decreased.
11. A recombinant bacterium of claim 1 , wherein the bacterium comprises:
a) pCD1
b) a relA inactivating mutation,
c) a spoT inactivating mutation,
d) a ΔlacZ::TT araC P BAD spoT mutation, and
e) a araC P BAD crp mutation such that the bacterium has regulated delayed attenuation.
12. A method of inducing a protective immune response in a host, the method comprising administering an immunogenic amount of a bacterium of claim 1 to the host.
13. A method of inducing a protective immune response in a host, the method comprising administering an immunogenic amount of a bacterium of claim 7 to the host.