title: Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects.
abstract: Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children's Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA.
authors.affiliation: Laboratorio de Parasitología Centro De Investigaciones Regional, "Dr. Hideo Noguchi" Autonomous University of Yucatan (UADY), Merida, Mexico.
authors.forename: Eric
authors.initials: E
authors.lastname: Dumonteil
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics (Section of Pediatric Tropical Medicine) and Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Bottazzi
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Department of Pediatrics (Section of Pediatric Tropical Medicine), National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhan
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Department of Pediatrics (Section of Pediatric Tropical Medicine), National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Heffernan
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics (Section of Pediatric Tropical Medicine) and Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Jones
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
authors.affiliation: Departamento de Biotecnología y Bioingeniería, Centro de Investigacion y de Estudios Avanzados - Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City, Mexico.
authors.forename: Jaime
authors.initials: J
authors.lastname: Ortega
authors.affiliation: Laboratorios de Biológicos y Reactivos de México (BIRMEX), Mexico City, Mexico.
authors.forename: Samuel Ponce
authors.initials: SP
authors.lastname: de Leon Rosales
authors.affiliation: Public Health Computational and Operations Research (PHICOR), University of Pittsburgh, Pittsburgh PA, USA.
authors.forename: Bruce Y
authors.initials: BY
authors.lastname: Lee
authors.affiliation: Public Health Computational and Operations Research (PHICOR), University of Pittsburgh, Pittsburgh PA, USA.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Bacon
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleischer
authors.affiliation: Eisai Co., Ltd, Tokyo, Japan.
authors.forename: B T
authors.initials: BT
authors.lastname: Slingsby
authors.affiliation: Instituto Carlos Slim de la Salud (ICSS), Mexico City, Mexico.
authors.forename: Miguel Betancourt
authors.initials: MB
authors.lastname: Cravioto
authors.affiliation: Instituto Carlos Slim de la Salud (ICSS), Mexico City, Mexico.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tapia-Conyer
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics (Section of Pediatric Tropical Medicine) and Molecular Virology & Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hotez
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D014355:Chagas Disease / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D016052:Protozoan Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C041524:aluminum sulfate