Abstract: Combinations of Trypanosoma cruzi polypeptides, fusion protein formed therefrom, and compositions and methods of use thereof for improved detection of antibodies against T. cruzi are disclosed. Preferred polypeptide combinations include two or more polypeptides selected from Table 1, or a variant or fragment thereof. In particularly preferred embodiments, the polypeptide combinations include the two polypeptide as paired in Table 2 or Table 3, or variants or fragments thereof. Preferably, the one, or more preferably both, of the polypeptides are antigenic to T. cruzi antibodies. The polypeptide combination can unfused or fused for form fusion proteins. Methods of using the disclosed compositions, including methods of detecting anti-T. cruzi antibodies, diagnosing T. cruzi infections, and monitoring disease status and treatment efficacy are also provided.

Abstract: This disclosure describes, in one aspect, a composition that includes a transgenic pathogen that expresses a heterologous pathogen associated molecular pattern (PAMP). In some embodiments, the pathogen may be attenuated. In some embodiments, the pathogen can include T. cruzi. In another aspect, this disclosure describes a method of treating an infection in a subject. Generally, the method includes administering to the subject, in an amount effective to treat the infection, a pathogen genetically modified to express a pathogen-associated molecular pattern (PAMP) not natively expressed by the pathogen.

Abstract: This disclosure describes, in one aspect, a composition that includes a transgenic pathogen that expresses a heterologous pathogen associated molecular pattern (PAMP). In some embodiments, the pathogen may be attenuated. In some embodiments, the pathogen can include T. cruzi. In another aspect, this disclosure describes a method of treating an infection in a subject. Generally, the method includes administering to the subject, in an amount effective to treat the infection, a pathogen genetically modified to express a pathogen-associated molecular pattern (PAMP) not natively expressed by the pathogen.

Abstract: A sensitive, multicomponent diagnostic test for infection with T. cruzi, the causative agent of Chagas disease, including methods of making and methods of use. Also provided is a method for screening T. cruzi polypeptides to identify antigenic polypeptides for inclusion as components of the diagnostic test, as well as compositions containing antigenic T. cruzi polypeptides.

Abstract: Molecular targets are identified in T. cruzi suitable for use in diagnosis of Chagas disease, drug development, and vaccines, including live vaccines.

Abstract: Polypeptide and polynucleotide vaccines effective to treat or prevent infection of a mammal, such as a dog, a cat, or a human, by a protozoan. Methods of treatment and prevention are also provided, including therapeutic administration of the vaccine to an infected mammal to prevent progression of infection to a chronic debilitating disease state. Preferred embodiments of the polynucleotide vaccine contain nucleotide coding regions that encode polypeptides that are surface-associated or secreted by T. cruzi. Optionally the efficacy of the polynucleotide vaccine is increased by inclusion of a nucleotide coding region encoding a cytokine. Preferred embodiments of the polypeptide vaccine include immunogenic peptides that contain membrane transducing sequences that allow the polypeptides to translocate across a mammalian cell membrane.