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.

Financial & competing interests disclosure

Michael Heffernan is a co-inventor on three patent applications pertaining to the pH-sensitive microparticles discussed in this manuscript. Several of the authors are involved in various aspects of the development and possible future manufacture of a potential vaccine currently in development against Chagas disease. The Carlos Slim Institute of Health and the Southwest Electronic Energy Medical Research Institute are providing financial support for the Chagas disease vaccine initiative. Eisai Co., Ltd is providing access to the E6020 adjuvant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

cGMP: Current good manufacturing practice; GLP: Good laboratory practice.

Affiliations

  • • Eric Dumonteil

    Laboratorio de Parasitología Centro De Investigaciones Regional, “Dr. Hideo Noguchi” Autonomous University of Yucatan (UADY), Merida, Mexico

  • • Maria Elena Bottazzi

    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

  • • Bin Zhan

    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

  • • Michael J Heffernan

    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

  • • Kathryn Jones

    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

  • • Jesus G Valenzuela

    Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA

  • • Shaden Kamhawi

    Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA

  • • Jaime Ortega

    Departamento de Biotecnología y Bioingeniería, Centro de Investigacion y de Estudios Avanzados - Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City, Mexico

  • • Samuel Ponce de Leon Rosales

    Laboratorios de Biológicos y Reactivos de México (BIRMEX), Mexico City, Mexico

  • • Bruce Y Lee

    Public Health Computational and Operations Research (PHICOR), University of Pittsburgh, Pittsburgh PA, USA

  • • Kristina M Bacon

    Public Health Computational and Operations Research (PHICOR), University of Pittsburgh, Pittsburgh PA, USA

  • • Bernhard Fleischer

    Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany

  • • BT Slingsby

    Eisai Co., Ltd, Tokyo, Japan

  • • Miguel Betancourt Cravioto

    Instituto Carlos Slim de la Salud (ICSS), Mexico City, Mexico

  • • Roberto Tapia-Conyer

    Instituto Carlos Slim de la Salud (ICSS), Mexico City, Mexico

  • • Peter J Hotez

    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

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