Attenuated uracil auxotroph of an apicomplexan and use thereof
Uracil auxotroph mutants of apicomplexans are provided which lack a functional carbamoyl phosphate synthase II (CPSII) enzyme. Also provided are T. gondii autoxtroph mutants which express exogenous antigens, and methods of protecting an animal against a T. gondii and non- T. gondii disease.
1. An attenuated uracil auxotroph mutant of Toxoplasma gondii comprising a nucleic acid molecule encoding an exogenous protein, wherein the exogenous protein is a non- Toxoplasma gondii bacterial, fungal, parasitic or tumor antigen, a protein that produces a non- Toxoplasma gondii antigen, a therapeutic antibody, an interferon, blood factor, insulin, erythropoietin, blood clotting factor, asparaginase, catalase, lipase, or tissue plasminogen activator.
2. The mutant of claim 1 , wherein said mutant lacks a functional carbamoyl phosphate synthetase II enzyme.
3. A vaccine for protection against infection by T. gondii and a non- T. gondii disease comprising the mutant of claim 1 in admixture with a pharmaceutically acceptable carrier.
4. The vaccine of claim 3 , wherein said vaccine is formulated for peritoneal, oral, topical, or intravenous administration.
5. A method for generating an immune response in an animal comprising administering to an animal an effective amount of the mutant of claim 1 so that an immune response to Toxoplasma gondii or non- T. gondii antigen is generated.
6. A method for identifying an effector of a human therapeutic target protein or enzyme comprising contacting the mutant of claim with an effector and determining whether the effector inhibits or activates the human therapeutic target protein or enzyme.
7. A method for sensing a host cell environment or specific molecules present or absent in the host cell environment comprising administering the mutant of claim 1 to a subject and determining the host cell environment or presence or absence of specific molecules in the host cell environment.
8. The method of claim 7 , wherein the molecule is a pyrimidine.