title: Expression, purification, immunogenicity, and protective efficacy of a recombinant Tc24 antigen as a vaccine against Trypanosoma cruzi infection in mice.
abstract: The Tc24 calcium binding protein from the flagellar pocket of Trypanosoma cruzi is under evaluation as a candidate vaccine antigen against Chagas disease. Previously, a DNA vaccine encoding Tc24 was shown to be an effective vaccine (both as a preventive and therapeutic intervention) in mice and dogs, as evidenced by reductions in T. cruzi parasitemia and cardiac amastigotes, as well as reduced cardiac inflammation and increased host survival. Here we developed a suitable platform for the large scale production of recombinant Tc24 (rTc24) and show that when rTc24 is combined with a monophosphoryl-lipid A (MPLA) adjuvant, the formulated vaccine induces a Th1-biased immune response in mice, comprised of elevated IgG2a antibody levels and interferon-gamma levels from splenocytes, compared to controls. These immune responses also resulted in statistically significant decreased T. cruzi parasitemia and cardiac amastigotes, as well as increased survival following T. cruzi challenge infections, compared to controls. Partial protective efficacy was shown regardless of whether the antigen was expressed in Escherichia coli or in yeast (Pichia pastoris). While mouse vaccinations will require further modifications in order to optimize protective efficacy, such studies provide a basis for further evaluations of vaccines comprised of rTc24, together with alternative adjuvants and additional recombinant antigens.
authors.affiliation: Laboratorio de Parasitología, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán, 97000 Mérida, Yucatán, Mexico.
authors.forename: Viridiana
authors.initials: V
authors.lastname: Martinez-Campos
authors.affiliation: Laboratorio de Parasitología, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán, 97000 Mérida, Yucatán, Mexico.
authors.forename: Pedro
authors.initials: P
authors.lastname: Martinez-Vega
authors.affiliation: Laboratorio de Parasitología, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán, 97000 Mérida, Yucatán, Mexico.
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Ramirez-Sierra
authors.affiliation: Laboratorio de Parasitología, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán, 97000 Mérida, Yucatán, Mexico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Rosado-Vallado
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Seid
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Elissa M
authors.initials: EM
authors.lastname: Hudspeth
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Junfei
authors.initials: J
authors.lastname: Wei
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Zhuyun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Cliff
authors.initials: C
authors.lastname: Kwityn
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Molly
authors.initials: M
authors.lastname: Hammond
authors.affiliation: Departamento de Biotecnología y Bioingeniería, CINVESTAV-IPN, Av. IPN 2508 Col., San Pedro Zacatenco 07360, Mexico D.F., Mexico.
authors.forename: Jaime
authors.initials: J
authors.lastname: Ortega-López
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhan
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biology, Baylor University, Waco, TX 76798, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hotez
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biology, Baylor University, Waco, TX 76798, USA.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Bottazzi
authors.affiliation: Laboratorio de Parasitología, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán, 97000 Mérida, Yucatán, Mexico. Electronic address: oliver@uady.mx.
authors.forename: Eric
authors.initials: E
authors.lastname: Dumonteil
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control*; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008050:Lipid A / Q000008:administration & dosage; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D018512:Parasitemia / Q000517:prevention & control; D010843:Pichia / Q000235:genetics; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D018417:Th1 Cells / Q000276:immunology; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D008050:Lipid A; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D007371:Interferon-gamma
keywords: Antigen; Chagas disease; Pre-clinical; Production; Vaccine