TY - JOUR
T1 - Accelerating the development of a therapeutic vaccine for human Chagas disease
T2 - Rationale and prospects
AU - Dumonteil, Eric
AU - Bottazzi, Maria Elena
AU - Zhan, Bin
AU - Heffernan, Michael J.
AU - Jones, Kathryn
AU - Valenzuela, Jesus G.
AU - Kamhawi, Shaden
AU - Ortega, Jaime
AU - De Leon Rosales, Samuel Ponce
AU - Lee, Bruce Y.
AU - Bacon, Kristina M.
AU - Fleischer, Bernhard
AU - Slingsby, B. T.
AU - Cravioto, Miguel Betancourt
AU - Tapia-Conyer, Roberto
AU - Hotez, Peter J.
N1 - Funding Information:
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.
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
KW - Chagas disease
KW - Mesoamerica
KW - Mexico
KW - TSA-1
KW - Tc24
KW - Trypanosoma cruzi
KW - therapeutic vaccine
KW - trypomastigote antigen
KW - vaccine
UR - http://www.scopus.com/inward/record.url?scp=84869415260&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869415260&partnerID=8YFLogxK
U2 - 10.1586/erv.12.85
DO - 10.1586/erv.12.85
M3 - Review article
C2 - 23151163
AN - SCOPUS:84869415260
SN - 1476-0584
VL - 11
SP - 1043
EP - 1055
JO - Expert review of vaccines
JF - Expert review of vaccines
IS - 9
ER -