Epitope mapping of vaccine antigens Tc24 and TSA1 with antibodies from Trypanosoma cruzi-infected patients

Epitope mapping of vaccine antigens Tc24 and TSA1 with antibodies from Trypanosoma cruzi-infected patients

  • Minhas AMK, Marcus R, Virani SS, Shapiro MD, Mentz RJ, Echeverria LE, et al. Worldwide prevalence of Chagas cardiomyopathy—an analysis from the global burden of disease dataset. Infection. 2025;53:947–52.

    Article 
    PubMed 

    Google Scholar
     

  • Rassi A Jr, Rassi A, Marin-Neto JA. Chagas disease. Lancet. 2010;375:1388–402.

    Article 
    PubMed 

    Google Scholar
     

  • Rassi A Jr, Marin JAN, Rassi A. Chronic Chagas cardiomyopathy: a review of the main pathogenic mechanisms and the efficacy of aetiological treatment following the BENznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial. Mem Inst Oswaldo Cruz. 2017;112:224–35.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Frade AF, Guerin H, Nunes JPS, Silva L, Roda VMP, Madeira RP, et al. Cardiac and digestive forms of Chagas disease: an update on pathogenesis, genetics, and therapeutic targets. Mediat Inflamm. 2025;2025:8862004.

    Article 
    CAS 

    Google Scholar
     

  • Pecoul B, Batista C, Stobbaerts E, Ribeiro I, Vilasanjuan R, Gascon J, et al. The BENEFIT trial: where do we go from here? PLoS Negl Trop Dis. 2016;10:e0004343.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Viotti R, Vigliano C, Lococo B, Alvarez MG, Petti M, Bertocchi G, et al. Side effects of benznidazole as treatment in chronic Chagas disease: fears and realities. Exp Rev Anti-Infect Ther. 2009;7:157–63.

    Article 
    CAS 

    Google Scholar
     

  • Pinazo MJ, Muñoz J, Posada E, López-Chejade P, Gallego M, Ayala E, et al. Tolerance of benznidazole in treatment of Chagas’ disease in adults. Antimicrob Agents Chemother. 2010;54:4896–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Antinori S, Grande R, Bianco R, Traversi L, Cogliati C, Torzillo D, et al. High frequency of adverse reactions and discontinuation with benznidazole treatment for chronic Chagas disease in Milano, Italy. Clin Infect Dis. 2015;60:1873–5.

    Article 
    PubMed 

    Google Scholar
     

  • Forsyth CJ, Hernandez S, Olmedo W, Abuhamidah A, Traina MI, Sanchez DR, et al. Safety profile of nifurtimox for treatment of Chagas disease in the United States. Clin Infect Dis. 2016;63:1056–62.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dumonteil E, Bottazzi ME, Zhan B, Heffernan MJ, Jones K, Valenzuela JG, et al. Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects. Exp Rev Vaccines. 2012;11:1043–55.

    Article 
    CAS 

    Google Scholar
     

  • Krautz GM, Galvao LM, Cancado JR, Guevara Espinoza A, Ouaissi A, Krettli AU. Use of a 24-kilodalton Trypanosoma cruzi recombinant protein to monitor cure of human Chagas’ disease. J Clin Microbiol. 1995;33:2086–90.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ouaissi A, Aguirre T, Plumas Marty B, Piras M, Schoneck R, Gras Masse H, et al. Cloning and sequencing of a 24-kDa Trypanosoma cruzi-specific antigen released in association with membrane vesicles and defined by a monoclonal antibody. Biol Cell. 1992;75:11–17.

  • Wrightsman RA, Dawson BD, Fouts DL, Manning JE. Identification of immunodominant epitopes in Trypanosoma cruzi trypomastigote surface antigen-1 protein that mask protective epitopes. J Immunol. 1994;153:3148–54.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Seid CA, Jones KM, Pollet J, Keegan B, Hudspeth E, Hammond M, et al. Cysteine mutagenesis improves the production without abrogating antigenicity of a recombinant protein vaccine candidate for human Chagas disease. Hum Vaccines Immunother. 2017;13:621–33.

    Article 

    Google Scholar
     

  • Biter AB, Weltje S, Hudspeth EM, Seid CA, McAtee CP, Chen WH, et al. Characterization and stability of Trypanosoma cruzi 24-C4 (Tc24-C4), a candidate antigen for a therapeutic vaccine against Chagas disease. J Pharm Sci. 2018;107:1468–73.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dzul-Huchim VM, Ramírez-Sierra MJ, Martínez-Vega PP, Rosado-Vallado ME, Arana-Argaez VE, Ortega-López J, et al. 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. 2022;16:e0010258.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Barry MA, Wang Q, Jones KM, Heffernan MJ, Buhaya MH, Beaumier CM, et al. A therapeutic nanoparticle vaccine against Trypanosoma cruzi in a BALB/c mouse model of Chagas disease. Hum Vaccines Immunother. 2016;12:976–87.

    Article 

    Google Scholar
     

  • de la Cruz JJ, Villanueva-Lizama L, Dzul-Huchim V, Ramírez-Sierra MJ, Martínez-Vega P, Rosado-Vallado M, et al. Production of recombinant TSA-1 and evaluation of its potential for the immuno-therapeutic control of Trypanosoma cruzi infection in mice. Hum Vaccines Immunother. 2019;15:210–9.

    Article 

    Google Scholar
     

  • Martínez-Campos V, Martínez-Vega P, Ramírez-Sierra MJ, Rosado-Vallado M, Seid CA, Hudspeth EM, et al. Expression, purification, immunogenicity, and protective efficacy of a recombinant Tc24 antigen as a vaccine against Trypanosoma cruzi infection in mice. Vaccine. 2015;33:4505–12.

    Article 
    PubMed 

    Google Scholar
     

  • Cruz-Chan JV, Villanueva-Lizama LE, Versteeg L, Damania A, Villar MJ, González-López C, et al. Vaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection. Sci Rep. 2021;11:3222.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jones K, Versteeg L, Damania A, Keegan B, Kendricks A, Pollet J, et al. Vaccine-linked chemotherapy improves benznidazole efficacy for acute Chagas disease. Infect Immun. 2018;86:e00876–17.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dumonteil E, Herrera C, Marx PA. Safety and preservation of cardiac function following therapeutic vaccination against Trypanosoma cruzi in rhesus macaques. J Microbiol Immunol Infect. 2023;56:400–7.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dumonteil E, Herrera C, Tu W, Goff K, Fahlberg M, Haupt E, et al. Safety and immunogenicity of a recombinant vaccine against Trypanosoma cruzi in Rhesus macaques. Vaccine. 2020;38:4584–91.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dumonteil E, Tu W, Desale H, Goff K, Marx P, Ortega-Lopez J, et al. Immunoglobulin and T cell receptor repertoire changes induced by a prototype vaccine against Chagas disease in naive rhesus macaques. J Biomed Sci. 2024;31:58.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Calderón-Quintal JA, Teh-Poot CF, Pech Piste LM, Martinez-Vega PP, Dzul-Huchim V, Torres-Acosta F et al. Randomized field trial of a therapeutic vaccine against Trypanosoma cruzi natural infection in dogs and correlates for efficacy. NPJ Vaccines 2025;11:18.

  • Villanueva-Lizama L, Cruz-Chan JV, Cetina-Aguilar AC, Herrera-Sánchez LF, Rodríguez-Pérez JM, Rosado-Vallado ME, et al. Trypanosoma cruzi vaccine candidate antigens Tc24 and TSA-1 recall memory immune response associated with HLA-A and –B supertypes in Chagasic chronic patients from Mexico. PLoS Negl Trop Dis. 2018;12:e0006240.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zingales B, Andrade SG, Briones MR, Campbell DA, Chiari E, Fernandes O, et al. A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI. Mem Inst Oswaldo Cruz. 2009;104:1051–4.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zingales B, Miles MA, Moraes CB, Luquetti A, Guhl F, Schijman AG, et al. Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity. Mem Inst Oswaldo Cruz. 2014;109:828–33.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arnal A, Villanueva-Lizama L, Teh-Poot C, Herrera C, Dumonteil E. Extent of polymorphism and selection pressure on the Trypanosoma cruzi vaccine candidate antigen Tc24. Evol Appl. 2020;13:2663–72.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Knight JM, Zingales B, Bottazzi ME, Hotez P, Zhan B. Limited antigenic variation in the Trypanosoma cruzi candidate vaccine antigen TSA-1. Parasite Immunol. 2014;36:708–12.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Buekens P, Cafferata ML, Alger J, Althabe F, Belizan JM, Bustamante N, et al. Congenital transmission of Trypanosoma cruzi in Argentina, Honduras, and Mexico: an observational prospective study. Am J Trop Med Hyg. 2018;98:478–85.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Majeau A, Dumonteil E, Herrera C. Identification of highly conserved Trypanosoma cruzi antigens for the development of a universal serological diagnostic assay. Emerg Micro Infect. 2024;13:2315964.

    Article 

    Google Scholar
     

  • Meng EC, Goddard TD, Pettersen EF, Couch GS, Pearson ZJ, Morris JH, et al. UCSF ChimeraX: tools for structure building and analysis. Protein Sci. 2023;32:e4792.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Khan T, Rahman M, Ahmed I, Al Ali F, Jithesh PV, Marr N. Human leukocyte antigen class II gene diversity tunes antibody repertoires to common pathogens. Front Immunol. 2022;13:856497.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Villanueva-Lizama L, Teh-Poot C, Majeau A, Herrera C, Dumonteil E. Molecular genotyping of Trypanosoma cruzi by next-generation sequencing of the mini-exon gene reveals infections with multiple parasite DTUs in Chagasic patients from Yucatan, Mexico. J Infect Dis. 2019;219:1980–8.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Majeau A, Herrera C, Dumonteil E. An improved approach to Trypanosoma cruzi molecular genotyping by next-generation sequencing of the mini-exon gene. Methods Mol Biol. 2019;1955:47–60.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Crooks GE, Hon G, Chandonia J-M, Brenner SE. WebLogo: a sequence logo generator. Genome Res. 2004;14:1188–90.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chiurillo MA, Cortez DR, Lima FM, Cortez C, Ramirez JL, Martins AG, et al. The diversity and expansion of the trans-sialidase gene family is a common feature in Trypanosoma cruzi clade members. Infect Genet Evol. 2016;37:266–74.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Freitas LM, dos Santos SL, Rodrigues-Luiz GF, Mendes TA, Rodrigues TS, Gazzinelli RT, et al. Genomic analyses, gene expression and antigenic profile of the trans-sialidase superfamily of Trypanosoma cruzi reveal an undetected level of complexity. PLoS ONE. 2011;6:e25914.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dumonteil E, Herrera C. The case for the development of a Chagas disease vaccine: Why? How? When? Trop Med Infect Dis. 2021;6:16.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carlier Y, Dumonteil E, Herrera C, Waleckx E, Tibayrenc M, Buekens P et al. Coinfection by multiple Trypanosoma cruzi clones: a new perspective on host-parasite relationship with consequences for pathogenesis and management of Chagas disease. Microbiol Mol Biol Rev 2025;89:e0024224.

  • Desale H, Tu W, Goff K, Marx PA, Herrera C, Dumonteil E. PBMC transcriptomic signatures reflect Trypanosoma cruzi strain diversity and trained immunity in chronically infected macaques. JCI Insight. 2025;10:e186003.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dumonteil E, Desale H, Tu W, Hernández-Cuevas N, Shroyer M, Goff K, et al. Intra-host Trypanosoma cruzi strain dynamics shape disease progression: the missing link in Chagas disease pathogenesis. Microbiol Spectr. 2023;11:e0423622.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jager AV, Muia RP, Campetella O. Stage-specific expression of Trypanosoma cruzi trans-sialidase involves highly conserved 3’ untranslated regions. FEMS Microbiol Lett. 2008;283:182–8.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Maldonado RA, Mirzoeva S, Godsel LM, Lukas TJ, Goldenberg S, Watterson DM, et al. Identification of calcium-binding sites in the trypanosome flagellar calcium-acyl switch protein. Mol Biochem Parasitol. 1999;101:61–70.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Colli W. Trans-sialidase: a unique enzyme activity discovered in the protozoan Trypanosoma cruzi. FASEB J. 1993;7:1257–64.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Alves MJ, Colli W. Role of the gp85/trans-sialidase superfamily of glycoproteins in the interaction of Trypanosoma cruzi with host structures. Subcell Biochem. 2008;47:58–69.

    Article 
    PubMed 

    Google Scholar
     

  • Teixeira AAR, Carnero LR, Kuramoto A, Tang FHF, Gomes CH, Pereira NB, et al. A refined genome phage display methodology delineates the human antibody response in patients with Chagas disease. iScience. 2021;24:102540.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wizel B, Nunes M, Tarleton RL. Identification of Trypanosoma cruzi trans-sialidase family members as targets of protective CD8+ TC1 responses. J Immunol. 1997;159:6120–30.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Martin DL, Weatherly DB, Laucella SA, Cabinian MA, Crim MT, Sullivan S, et al. CD8+ T-Cell responses to Trypanosoma cruzi are highly focused on strain-variant trans-sialidase epitopes. PLoS Pathog. 2006;2:e77.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pitcovsky TA, Mucci J, Alvarez P, Leguizamon MS, Burrone O, Alzari PM, et al. Epitope mapping of trans-sialidase from Trypanosoma cruzi reveals the presence of several cross-reactive determinants. Infect Immun. 2001;69:1869–75.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pitcovsky TA, Buscaglia CA, Mucci J, Campetella O. A functional network of intramolecular cross-reacting epitopes delays the elicitation of neutralizing antibodies to Trypanosoma cruzi trans-sialidase. J Infect Dis. 2002;186:397–404.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pacini MF, Perdomini A, Bulfoni Balbi C, Dinatale B, Herrera FE, Perez AR, et al. The high identity of the Trypanosoma cruzi Group-I of trans-sialidases points them as promising vaccine immunogens. Proteins. 2023;91:1444–60.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mejia R, Verocai GG, Mosley IA, Zhan B, Vongthavaravat L, Busselman RE, et al. Evaluation of a novel Tc-24 recombinant antigen ELISA for serologic testing for Trypanosoma cruzi in dogs. Vet Med Sci. 2025;11:e70570.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Calderón-Quintal JA, Escalante-Talavera MJ, Teh-Poot C, Carrera-Campellone MN, Martínez-Vega PP, Dzul-Huchim V, et al. Natural infection of Trypanosoma cruzi in client-owned dogs from rural Yucatan, Mexico. Sci Rep. 2025;15:10263.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Majeau A, Murphy L, Herrera C, Dumonteil E. Assessing Trypanosoma cruzi parasite diversity through comparative genomics: implications for disease epidemiology and diagnostics. Pathogens. 2021;10:212.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar