{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:57:06Z","timestamp":1791417426806,"version":"4.3.3"},"reference-count":96,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["R01AI136031"],"award-info":[{"award-number":["R01AI136031"]}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["R44AI172437"],"award-info":[{"award-number":["R44AI172437"]}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["R21AI178318"],"award-info":[{"award-number":["R21AI178318"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Chagas disease (CD) is a global health concern, with no existing therapies to prophylactically treat adults traveling to endemic countries or those who may already be infected with Trypanosoma cruzi. The economic burden of Chagas cardiomyopathy and heart failure, due to healthcare costs and lost productivity from premature deaths, provides a strong rationale for investment in the development of immune therapies against CD. Vaccine efficacy is proposed to depend heavily on the induction of a robust Th1 response for the clearance of intracellular pathogens like T. cruzi. In this review, updated information on the efforts for vaccine development against CD is provided.<\/jats:p>","DOI":"10.3390\/pathogens14020124","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T04:01:39Z","timestamp":1738209699000},"page":"124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["An Update on Vaccines Against Trypanosoma cruzi and Chagas Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3453-2369","authenticated-orcid":false,"given":"Nisha J.","family":"Garg","sequence":"first","affiliation":[{"name":"Department of Microbiology & Immunology, University of Texas Medical Branch (UTMB), Galveston, TX 77555-1070, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch (UTMB), Galveston, TX 77555-1070, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1146\/annurev-pathol-020117-043711","article-title":"Pathology and pathogenesis of chagas heart disease","volume":"14","author":"Bonney","year":"2020","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_2","unstructured":"World Health Organization (2010). Chagas Disease: Control and Elimination, UNDP\/World Bank\/WHO. Available online: http:\/\/apps.who.int\/gb\/ebwha\/pdf_files\/WHA63\/A63_17-en.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7414","DOI":"10.1016\/j.vaccine.2010.08.104","article-title":"Effect of a combination DNA vaccine for the prevention and therapy of Trypanosoma cruzi infection in mice: Role of CD4+ and CD8+ T cells","volume":"28","author":"VanWynsberghe","year":"2010","journal-title":"Vaccine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1590\/S0074-02762009000900005","article-title":"Current epidemiological trends for Chagas disease in Latin America and future challenges in epidemiology, surveillance and health policy","volume":"104","author":"Moncayo","year":"2009","journal-title":"Mem. Inst. Oswaldo Cruz."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/S1473-3099(13)70002-1","article-title":"Global economic burden of Chagas disease: A computational simulation model","volume":"13","author":"Lee","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lee, B.Y., Bacon, K.M., Connor, D.L., Willig, A.M., and Bailey, R.R. (2010). The potential economic value of a Trypanosoma cruzi (Chagas disease) vaccine in Latin America. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000916"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/j.1365-3024.2009.01108.x","article-title":"The role of parasite persistence in pathogenesis of Chagas heart disease","volume":"31","author":"Gutierrez","year":"2009","journal-title":"Parasite Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Vellozo, N.S., Matos-Silva, T.C., and Lopes, M.F. (2023). Immunopathogenesis in Trypanosoma cruzi infection: A role for suppressed macrophages and apoptotic cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1244071"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lewis, M.D., Francisco, A.F., Jayawardhana, S., Langston, H., Taylor, M.C., and Kelly, J.M. (2018). Imaging the development of chronic Chagas disease after oral transmission. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-29564-7"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"24085","DOI":"10.1074\/jbc.M412802200","article-title":"The adipocyte as an important target cell for Trypanosoma cruzi infection","volume":"280","author":"Combs","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.micinf.2011.06.002","article-title":"Evidence for Trypanosoma cruzi in adipose tissue in human chronic chagas disease","volume":"13","author":"Ferreira","year":"2011","journal-title":"Microbes Infect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e34039","DOI":"10.7554\/eLife.34039","article-title":"Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure","volume":"7","author":"Padilla","year":"2018","journal-title":"Elife"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1161\/CIRCULATIONAHA.106.624296","article-title":"Pathogenesis of chronic Chagas heart disease","volume":"115","author":"Maciel","year":"2007","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1080\/14760584.2021.1969230","article-title":"Oxidative stress implications for therapeutic vaccine development against Chagas disease","volume":"20","author":"Choudhuri","year":"2021","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4993452","DOI":"10.1155\/2021\/4993452","article-title":"The oxidative stress and chronic inflammatory process in Chagas disease: Role of exosomes and contributing genetic factors","volume":"2021","author":"Maldonado","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ijcard.2006.04.046","article-title":"Oxidative stress in chronic cardiopathy associated with Chagas disease","volume":"116","author":"Pedrosa","year":"2007","journal-title":"Int. J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s40588-018-0081-2","article-title":"Pathogenesis of chronic Chagas disease: Macrophages, mitochondria, and oxidative stress","volume":"5","author":"Lopez","year":"2018","journal-title":"Curr. Clin. Microbiol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102770","DOI":"10.1016\/j.parint.2023.102770","article-title":"Oxidative stress evaluation in patients with chronic Chagas disease","volume":"96","author":"Gatto","year":"2023","journal-title":"Parasitol. Int."},{"key":"ref_19","first-page":"9081813","article-title":"Potential role of antioxidants as adjunctive therapy in Chagas disease","volume":"2020","author":"Serrano","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wan, X., and Garg, N.J. (2021). Sirtuin control of mitochondrial dysfunction, oxidative stress, and inflammation in Chagas disease models. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.693051"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Choudhuri, S., Chowdhury, I.H., and Garg, N.J. (2020). Mitochondrial regulation of macrophage response against pathogens. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.622602"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rios, L., Campos, E.E., Menon, R., Zago, M.P., and Garg, N.J. (2020). Epidemiology and pathogenesis of maternal-fetal transmission of Trypanosoma cruzi and a case for vaccine development against congenital chagas disease. Biochim. Biophys. Acta Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2019.165591"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Maldonado, E., Morales-Pison, S., Urbina, F., and Solari, A. (2022). Vaccine design against Chagas disease focused on the use of nucleic acids. Vaccines, 10.","DOI":"10.3390\/vaccines10040587"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100972","DOI":"10.1016\/j.lanmic.2024.100972","article-title":"Challenges and advancements in the development of vaccines and therapies against Chagas disease","volume":"5","author":"Pinazo","year":"2024","journal-title":"Lancet Microbe"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Farani, P.S.G., Jones, K.M., and Poveda, C. (2024). Treatments and the perspectives of developing a vaccine for Chagas disease. Vaccines, 12.","DOI":"10.3390\/vaccines12080870"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez-Toloza, G., and Ferreira, A. (2017). Trypanosoma cruzi evades the complement system as an efficient strategy to survive in the mammalian host: The specific roles of host\/parasite molecules and trypanosoma cruzi calreticulin. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01667"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1093\/emboj\/19.7.1476","article-title":"Highly purified glycosylphosphatidylinositols from Trypanosoma cruzi are potent proinflammatory agents","volume":"19","author":"Almeida","year":"2000","journal-title":"EMBO J."},{"key":"ref_28","unstructured":"Gavins, F.N.E., and Stokes, K.Y. (2016). Trypanosoma cruzi and Chagas disease: Innate immunity, ROS, and cardiovascular system. Vascular Responses to Pathogens, Academic Press\/Elsevier Inc."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Cronemberger-Andrade, A., Xander, P., Soares, R.P., Pessoa, N.L., Campos, M.A., Ellis, C.C., Grajeda, B., Ofir-Birin, Y., Almeida, I.C., and Regev-Rudzki, N. (2020). Trypanosoma cruzi-infected human macrophages shed proinflammatory extracellular vesicles that enhance host-cell invasion via toll-like receptor 2. Front. Cell Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00099"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Koo, S.J., Szczesny, B., Wan, X., Putluri, N., and Garg, N.J. (2018). Pentose phosphate shunt modulates reactive oxygen species and nitric oxide production controlling Trypanosoma cruzi in macrophages. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00202"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Koo, S.J., and Garg, N.J. (2019). Metabolic programming of macrophage functions and pathogens control. Redox Biol., 24.","DOI":"10.1016\/j.redox.2019.101198"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cerb\u00e1n, F.M., Stempin, C.C., Volpini, X., Carrera Silva, E.A., Gea, S., and Motran, C.C. (2020). Signaling pathways that regulate Trypanosoma cruzi infection and immune response. Biochim. Biophys. Acta-Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2020.165707"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Macaluso, G., Grippi, F., Di Bella, S., Blanda, V., Gucciardi, F., Torina, A., Guercio, A., and Cannella, V. (2023). A review on the immunological response against Trypanosoma cruzi. Pathogens, 12.","DOI":"10.3390\/pathogens12020282"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0165-2478(00)00205-4","article-title":"CD4+ Th1 but not Th2 clones efficiently activate macrophages to eliminate Trypanosoma cruzi through a nitric oxide dependent mechanism","volume":"73","author":"Rodrigues","year":"2000","journal-title":"Immunol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1128\/IAI.68.1.197-204.2000","article-title":"Involvement of CD4+ Rh1 cells in systemic immunity protective against primary and secondary challenges with Trypanosoma cruzi","volume":"68","author":"Hoft","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.pt.2020.08.001","article-title":"A-gal-based vaccines: Advances, opportunities, and perspectives","volume":"36","year":"2020","journal-title":"Trends Parasitol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.pt.2019.08.006","article-title":"Understanding CD8+T cell immunity to Trypanosoma cruzi and how to improve it","volume":"35","author":"Montes","year":"2019","journal-title":"Trends Parasitol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"105242","DOI":"10.1016\/j.actatropica.2019.105242","article-title":"Immunological exhaustion and functional profile of CD8+T lymphocytes as cellular biomarkers of therapeutic efficacy in chronic Chagas disease patients","volume":"202","author":"Egui","year":"2020","journal-title":"Acta Trop."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/pim.12107","article-title":"Immunoregulatory networks in human Chagas disease","volume":"36","author":"Dutra","year":"2014","journal-title":"Parasite Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Medina-Rinc\u00f3n, G.J., Gallo-Bernal, S., Jim\u00e9nez, P.A., Cruz-Saavedra, L., Ram\u00edrez, J.D., Rodr\u00edguez, M.J., Medina-Mur, R., D\u00edaz-Nassif, G., Valderrama-Achury, M.D., and Medina, H.M. (2021). Molecular and clinical aspects of chronic manifestations in Chagas disease: A state-of-the-art review. Pathogens, 10.","DOI":"10.3390\/pathogens10111493"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.pt.2021.11.004","article-title":"Live attenuated vaccines, a favorable strategy to provide long-term immunity against protozoan diseases","volume":"38","author":"Solana","year":"2022","journal-title":"Trends Parasitol."},{"key":"ref_42","first-page":"39","article-title":"Evaluation of an attenuated Trypanosoma cruzi strain in rats. Analysis of survival, parasitemia and tissue damage","volume":"53","author":"Revelli","year":"1993","journal-title":"Medicina"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"143","DOI":"10.4269\/ajtmh.1993.49.143","article-title":"Field trial of vaccination against American Trypanosomiasis (Chagas\u2019 disease) in dogs","volume":"49","author":"Basombrio","year":"1993","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.imbio.2014.10.003","article-title":"Experimental Chagas disease in balb\/c mice previously vaccinated with T. rangeli. II. The innate immune response shows immunological memory: Reality or fiction?","volume":"220","author":"Basso","year":"2015","journal-title":"Immunobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.vetimm.2013.10.011","article-title":"Vaccination with Trypanosoma rangeli induces resistance of guinea pigs to virulent Trypanos Cruzi","volume":"157","author":"Basso","year":"2014","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gupta, S., Salgado-Jimenez, B., Lokugamage, N., Vazquez-Chagoyan, J.C., and Garg, N.J. (2019). Tcg2\/Tcg4 DNA vaccine induces th1 immunity against acute Trypanosoma cruzi infection: Adjuvant and antigenic effects of heterologous T. rangeli booster immunization. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01456"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1586\/14760584.2015.989989","article-title":"Gene-deleted live-attenuated Trypanosoma cruzi parasites as vaccines to protect against Chagas disease","volume":"14","author":"Ferreira","year":"2015","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3293","DOI":"10.4049\/jimmunol.158.7.3293","article-title":"Delivery by Trypanosoma cruzi of proteins into the MHC class I antigen processing and presentation pathway","volume":"158","author":"Garg","year":"1997","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"da Costa, K.M., Marques da Fonseca, L., Dos Reis, J.S., Santos, M., Previato, J.O., Mendonca-Previato, L., and Freire-de-Lima, L. (2021). Trypanosoma cruzi trans-sialidase as a potential vaccine target against Chagas disease. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.768450"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"105168","DOI":"10.1016\/j.actatropica.2019.105168","article-title":"Immunity and vaccine development efforts against Trypanosoma cruzi","volume":"200","author":"Rios","year":"2019","journal-title":"Acta Trop."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6245","DOI":"10.1128\/IAI.72.11.6245-6254.2004","article-title":"Utility of Trypanosoma cruzi sequence database for the identification of potential vaccine candidates: In silico and in vitro screening","volume":"72","author":"Bhatia","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1128\/CVI.00144-08","article-title":"Previously unrecognized vaccine candidates control Trypanosoma cruzi infection and immunopathology in mice","volume":"15","author":"Bhatia","year":"2008","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Albaqami, F.F., Altharawi, A., Althurwi, H.N., and Alharthy, K.M. (2024). From proteome to candidate vaccines: Target discovery and molecular dynamics-guided multi-epitope vaccine engineering against kissing bug. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1413893"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1016\/j.vaccine.2014.04.026","article-title":"A synthetic peptide from Trypanosoma cruzi mucin-like associated surface protein as candidate for a vaccine against Chagas disease","volume":"32","author":"Serna","year":"2014","journal-title":"Vaccine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1128\/IAI.01163-07","article-title":"Oral vaccination with Salmonella enterica as a cruzipain-DNA delivery system confers protective immunity against Trypanosoma cruzi","volume":"76","author":"Cazorla","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7046","DOI":"10.1016\/j.vaccine.2006.07.006","article-title":"The genetic immunization with paraflagellar rod protein-2 fused to the hsp70 confers protection against late Trypanosoma cruzi infection","volume":"24","author":"Morell","year":"2006","journal-title":"Vaccine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.molimm.2012.05.021","article-title":"Trypanosoma cruzi paraflagellar rod proteins 2 and 3 contain immunodominant CD8+T-cell epitopes that are recognized by cytotoxic t cells from chagas disease patients","volume":"52","author":"Egui","year":"2012","journal-title":"Mol. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.1016\/S0264-410X(03)00121-X","article-title":"Genetic immunization with Lyt1 or a pool of trans-sialidase genes protects mice from lethal Trypanosoma cruzi infection","volume":"21","author":"Fralish","year":"2003","journal-title":"Vaccine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1089\/hum.2004.15.878","article-title":"Protective immunity against Trypanosoma cruzi infection in a highly susceptible mouse strain after vaccination with genes encoding the amastigote surface protein-2 and trans-sialidase","volume":"15","author":"Vasconcelos","year":"2004","journal-title":"Hum. Gene Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1089\/hum.2013.218","article-title":"Adenovirus vector-induced CD8+T effector memory cell differentiation and recirculation, but not proliferation, are important for protective immunity against experimental Trypanosoma cruzi infection","volume":"25","author":"Vasconcelos","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Pereira, I.R., Vilar-Pereira, G., Marques, V., da Silva, A.A., Caetano, B., Moreira, O.C., Machado, A.V., Bruna-Romero, O., Rodrigues, M.M., and Gazzinelli, R.T. (2015). A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004594"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1002\/jcb.27608","article-title":"A Therapeutical effects of vaccine from Trypanosoma cruzi amastigote surface protein 2 by simultaneous inoculation with live parasites","volume":"120","author":"Ribeiro","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41541-019-0107-7","article-title":"A prophylactic \u03b1-gal-based glycovaccine effectively protects against murine acute chagas disease","volume":"4","author":"Portillo","year":"2019","journal-title":"NPJ Vaccines"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Gupta, S., and Garg, N.J. (2010). Prophylactic efficacy of TcVac2 against Trypanosoma cruzi in mice. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000797"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Gupta, S., and Garg, N.J. (2013). TcVac3 induced control of Trypanosoma cruzi infection and chronic myocarditis in mice. PLOS ONE, 8.","DOI":"10.1371\/journal.pone.0059434"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Gupta, S., and Garg, N.J. (2015). A two-component DNA-prime\/protein-boost vaccination strategy for eliciting long-term, protective T cell immunity against Trypanosoma cruzi. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004828"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Chowdhury, I.H., Lokugamage, N., and Garg, N.J. (2020). Experimental nanovaccine offers protection against repeat exposures to Trypanosoma cruzi through activation of polyfunctional T cell response. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.595039"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lokugamage, N., Choudhuri, S., Davies, C., Chowdhury, I.H., and Garg, N.J. (2020). Antigen-based nano-immunotherapy controls parasite persistence, inflammatory and oxidative stress, and cardiac fibrosis, the hallmarks of chronic Chagas cardiomyopathy, in a mouse model of Trypanosoma cruzi infection. Vaccines, 8.","DOI":"10.3390\/vaccines8010096"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Aparicio-Burgos, J.E., Ochoa-Garcia, L., Zepeda-Escobar, J.A., Gupta, S., Dhiman, M., Martinez, J.S., de Oca-Jimenez, R.M., Val Arreola, M., Barbabosa-Pliego, A., and Vazquez-Chagoyan, J.C. (2011). Testing the efficacy of a multi-component DNA-prime\/DNA-boost vaccine against Trypanosoma cruzi infection in dogs. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001050"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Aparicio-Burgos, J.E., Zepeda-Escobar, J.A., de Oca-Jimenez, R.M., Estrada-Franco, J.G., Barbabosa-Pliego, A., Ochoa-Garcia, L., Alejandre-Aguilar, R., Rivas, N., Penuelas-Rivas, G., and Val-Arreola, M. (2015). Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003625"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1297-9716-44-15","article-title":"Specific humoral and cellular immunity induced by Trypanosoma cruzi DNA immunization in a canine model","volume":"44","author":"Zenteno","year":"2013","journal-title":"Vet. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41541-017-0010-z","article-title":"Engineered trivalent immunogen adjuvanted with a sting agonist confers protection against Trypanosoma cruzi infection","volume":"2","author":"Bivona","year":"2017","journal-title":"NPJ Vaccines"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1542\/pir.2022-005857","article-title":"Congenital Chagas disease","volume":"44","author":"Chancey","year":"2023","journal-title":"Pediatr. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.actatropica.2017.07.004","article-title":"Prevention of congenital Chagas disease by benznidazole treatment in reproductive-age women. An observational study","volume":"174","author":"Alvarez","year":"2017","journal-title":"Acta Trop."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ajpath.2022.11.010","article-title":"Effects of acute and chronic Trypanosoma cruzi infection on pregnancy outcomes in mice: Parasite transmission, mortality, delayed growth, and organ damage in pups","volume":"193","author":"Rios","year":"2023","journal-title":"Am. J. Pathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/s41541-023-00782-z","article-title":"Subunit nanovaccine elicited T cell functional activation controls Trypanosoma cruzi mediated maternal and placental tissue damage and improves pregnancy outcomes in mice","volume":"8","author":"Rios","year":"2023","journal-title":"NPJ Vaccines"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1128\/IAI.72.1.46-53.2004","article-title":"Immunotherapy of trypanosoma cruzi infection with DNA vaccines in mice","volume":"72","author":"Dumonteil","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1196\/annals.1428.098","article-title":"Therapeutic DNA vaccine against trypanosoma cruzi infection in dogs","volume":"1149","author":"Dumonteil","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1574-695X.2007.00251.x","article-title":"Comparative evaluation of therapeutic DNA vaccines against trypanosoma cruzi in mice","volume":"50","author":"Ouaissi","year":"2007","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.imlet.2005.11.015","article-title":"Control of trypanosoma cruzi infection and changes in t-cell populations induced by a therapeutic DNA vaccine in mice","volume":"103","author":"Dumonteil","year":"2006","journal-title":"Immunol. Lett."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1080\/21645515.2015.1119346","article-title":"A therapeutic nanoparticle vaccine against trypanosoma cruzi in a balb\/c mouse model of chagas disease","volume":"12","author":"Barry","year":"2016","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Barry, M.A., Versteeg, L., Wang, Q., Pollet, J., Zhan, B., Gusovsky, F., Bottazzi, M.E., Hotez, P.J., and Jones, K.M. (2019). A therapeutic vaccine prototype induces protective immunity and reduces cardiac fibrosis in a mouse model of chronic trypanosoma cruzi infection. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007413"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.jmii.2022.09.003","article-title":"Safety and preservation of cardiac function following therapeutic vaccination against trypanosoma cruzi in rhesus macaques","volume":"56","author":"Dumonteil","year":"2023","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1128\/CVI.00032-12","article-title":"Challenge of chronically infected mice with homologous trypanosoma cruzi parasites enhances the immune response but does not modify cardiopathy: Implications for the design of a therapeutic vaccine","volume":"20","year":"2013","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.2353\/ajpath.2006.060475","article-title":"Phenyl-alpha-tert-butyl nitrone reverses mitochondrial decay in acute chagas' disease","volume":"169","author":"Wen","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1016\/j.jacc.2010.02.030","article-title":"Phenyl-alpha-tert-butyl-nitrone and benzonidazole treatment controlled the mitochondrial oxidative stress and evolution of cardiomyopathy in chronic chagasic rats","volume":"55","author":"Wen","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Gupta, S., Smith, C., Auclair, S., Delgadillo Ade, J., and Garg, N.J. (2015). Therapeutic efficacy of a subunit vaccine in controlling chronic Trypanosoma cruzi infection and chagas disease is enhanced by glutathione peroxidase over-expression. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130562"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Dzul-Huchim, V.M., Ramirez-Sierra, M.J., Martinez-Vega, P.P., Rosado-Vallado, M.E., Arana-Argaez, V.E., Ortega-Lopez, J., Gusovsky, F., Dumonteil, E., Cruz-Chan, J.V., and Hotez, P. (2022). Vaccine-linked chemotherapy with a low dose of benznidazole plus a bivalent recombinant protein vaccine prevents the development of cardiac fibrosis caused by Trypanosoma cruzi in chronically-infected balb\/c mice. PLoS Negl. Trop. Dis., 16.","DOI":"10.1101\/2022.02.16.480638"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/s41579-019-0238-x","article-title":"Protozoan persister-like cells and drug treatment failure","volume":"17","author":"Barrett","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1177\/2051013614541440","article-title":"Liposomes as vaccine delivery systems: A review of the recent advances","volume":"2","author":"Schwendener","year":"2014","journal-title":"Ther. Adv. Vaccines"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"13225","DOI":"10.1002\/anie.202010282","article-title":"Biopolymer-based carriers for DNA vaccine design","volume":"60","author":"Franck","year":"2021","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Kheirvari, M., Liu, H., and Tumban, E. (2023). Virus-like particle vaccines and platforms for vaccine development. Viruses, 15.","DOI":"10.3390\/v15051109"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/978-1-4939-6869-5_15","article-title":"Bacteriophage t4 as a nanoparticle platform to display and deliver pathogen antigens: Construction of an effective anthrax vaccine","volume":"1581","author":"Tao","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1080\/14760584.2021.1893170","article-title":"Plant-made vaccines against parasites: Bioinspired perspectives to fight against chagas disease","volume":"20","author":"Dumonteil","year":"2021","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"165758","DOI":"10.1016\/j.bbadis.2020.165758","article-title":"State-of-the-art in host-derived biomarkers of Chagas disease prognosis and early evaluation of anti-Trypanosoma cruzi treatment response","volume":"1866","author":"Pinazo","year":"2020","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Choudhuri, S., Bhavnani, S.K., Zhang, W., Botelli, V., Barrientos, N., I\u00f1iguez, F., Zago, M.P., and Garg, N.J. (2021). Prognostic performance of peripheral blood biomarkers in identifying seropositive individuals at risk of developing clinically symptomatic Chagas cardiomyopathy. Microbiol. Spectr., 9.","DOI":"10.1128\/Spectrum.00364-21"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/2\/124\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:38:37Z","timestamp":1759919917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/2\/124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,30]]},"references-count":96,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["pathogens14020124"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14020124","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,30]]}}}