Augusto E. Bivona

University of Buenos Aires

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Emilio L. Malchiodi

University of Buenos Aires

Andrés Sánchez Alberti

Consejo Nacional de Investigaciones Científicas y Técnicas

Natacha Cerny

National University of Luján

Valeria P. Sülsen

University of Buenos Aires

Silvia I. Cazorla

Consejo Nacional de Investigaciones Científicas y Técnicas

Orlando G. Elso

University of Buenos Aires

César A.N. Catalán

National University of Tucumán

Celina Morales

University of Buenos Aires

Jimena Borgo

Consejo Nacional de Investigaciones Científicas y Técnicas

María Florencia Beer

Instituto de Química y Fisicoquímica Biológicas

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Consejo Nacional de Investigaciones Científicas y Técnicas

University of Buenos Aires

Instituto de Química y Fisicoquímica Biológicas

Institute of Astronomy and Space Physics

Universidad de la República

Helmholtz Centre for Infection Research

Fundación Ciencias Exactas y Naturales

Instituto de Estudios Universitarios

Medicina

University of Palermo

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Chagas disease vaccine design: the search for an efficient Trypanosoma cruzi immune-mediated control

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (2020)

Augusto E. Bivona Andrés Sánchez Alberti Natacha Cerny Sebastián Nicolás Trinitario Emilio L. Malchiodi

Chagas Disease

Vaccine efficacy

10.1016/j.bbadis.2019.165658

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Citations (59)

Oral Multicomponent DNA Vaccine Delivered by Attenuated Salmonella Elicited Immunoprotection Against American Trypanosomiasis

The Journal of Infectious Diseases (2014)

Silvia I. Cazorla Marina N. Matos Natacha Cerny Carlos Wong Ramírez Andrés Sánchez Alberti

We have reported that attenuated Salmonella (S) carrying plasmids encoding the cysteine protease cruzipain (Cz) protects against Trypanosoma cruzi infection. Here, we determined whether immunoprotection could be improved by the oral coadministration of 3 Salmonella carrying the plasmids that encode the antigens Cz, Tc52, and Tc24. SCz+STc52+STc24–immunized mice presented an increased antibody response against each antigen compared with those in the single antigen–immunized groups, as well as higher trypomastigotes antibody-mediated lyses and cell invasion inhibition compared with controls. SCz+STc52+STc24–immunized and –challenged mice rendered lower parasitemia. Weight loss after infection was detected in all mice except those in the SCz+STc52+STc24 group. Moreover, cardiomyopathy-associated enzyme activity was significantly lower in SCz+STc24+STc52–immunized mice compared with controls. Few or no abnormalities were found in muscle tissues of SCz+STc24+STc52–immunized mice, whereas controls presented with inflammatory foci, necrosis, and amastigote nests. We conclude that a multicomponent approach that targets several invasion and metabolic mechanisms improves protection compared with single-component vaccines.

Attenuated vaccine

10.1093/infdis/jiu480

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Citations (31)

Antitrypanosomal and Antileishmanial Activities

Springer eBooks (2018)

Andrés Sánchez Alberti Natacha Cerny Augusto E. Bivona Silvia I. Cazorla

10.1007/978-3-319-78274-4_8

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Citations (6)

Tc52 Amino-Terminal-Domain DNA Carried by Attenuated Salmonella enterica Serovar Typhimurium Induces Protection against a Trypanosoma cruzi Lethal Challenge

Infection and Immunity (2014)

Marina N. Matos Silvia I. Cazorla Augusto E. Bivona Celina Morales Carlos A. Guzmán

In this work we immunized mice with DNA encoding full-length Tc52 or its amino- or carboxy-terminal (N- and C-term, respectively) domain carried by attenuated Salmonella as a DNA delivery system. As expected, Salmonella-mediated DNA delivery resulted in low antibody titers and a predominantly Th1 response, as shown by the ratio of IgG2a/IgG1-specific antibodies. Despite modest expression of Tc52 in trypomastigotes, the antibodies elicited by vaccination were able to mediate lysis of the trypomastigotes in the presence of complement and inhibit their invasion of mammal cells in vitro. The strongest functional activity was observed with sera from mice immunized with Salmonella carrying the N-term domain (SN-term), followed by Tc52 (STc52), and the C-term domain (SC-term). All immunized groups developed strong cellular responses, with predominant activation of Th1 cells. However, mice immunized with SN-term showed higher levels of interleukin-10 (IL-10), counterbalancing the inflammatory reaction, and also strong activation of Tc52-specific gamma interferon-positive (IFN-γ(+)) CD8(+) T cells. In agreement with this, although all prototypes conferred protection against infection, immunization with SN-term promoted greater protection than that with SC-term for all parameters tested and slightly better protection than that with STc52, especially in the acute stage of infection. We conclude that the N-terminal domain of Tc52 is the section of the protein that confers maximal protection against infection and propose it as a promising candidate for vaccine development.

Salmonella enterica

10.1128/iai.02190-14

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Citations (25)

Challenges and advancements in the development of vaccines and therapies against Chagas disease

The Lancet Microbe (2024)

María‐Jesús Pinazo Emilio L. Malchiodi Jean‐Robert Ioset Augusto E. Bivona Kenneth J. Gollob

Chagas Disease

10.1016/j.lanmic.2024.100972

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Coadministration of cruzipain and GM-CSF DNAs, a new immunotherapeutic vaccine againstTrypanosoma cruziinfection

Human Vaccines & Immunotherapeutics (2015)

Natacha Cerny Andrés Sánchez Alberti Augusto E. Bivona Mauricio C. De Marzi Fernanda M. Frank

Therapeutic vaccine research and development are especially important in Chagas disease considering the characteristics of the chronic infection and the number of people in the Americas living with a parasite infection for decades. We have previously reported the efficacy of attenuated Salmonella enterica (S) carrying plasmid encoding cruzipain (SCz) to protect against Trypanosoma cruzi infection. In the present work we investigated whether Cz DNA vaccine immunotherapy could be effective in controlling an ongoing T. cruzi infection in mice. We here report the intramuscular administration of naked Cz DNA or the oral administration of Salmonella as Cz DNA delivery system as therapeutic vaccines in mice during acute or chronic infection. The coadministration of a plasmid encoding GM-CSF improved vaccine performance, indicating that the stimulation of innate immune cells is needed in the event of an ongoing infection. These therapeutic vaccines were able to address the response to a protective and sustained Th1 biased profile not only against Cz but also against a variety of parasite antigens. The combined therapeutic vaccine during the chronic phase of infection prevents tissue pathology as shown by a reduced level of enzyme activity characteristic of tissue damage and a tissue status compatible with normal tissue. The obtained results suggest that immunotherapy with Cz and GM-CSF DNAs, either alone or in combination with other drug treatments, may represent a promising alternative for Chagas disease therapy.

Chagas Disease

Chronic infection

10.1080/21645515.2015.1078044

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Citations (20)

[Changes in prolactin, cortisol and dehydroepiandrosterone during ergometric tests].

PubMed (1985)

Domenico Campisi Salvatore Paterna Cilluffo Mp G Montaina Augusto E. Bivona

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Oestrogen binding sites in fresh human aortic tissue.

PubMed (1987)

Domenico Campisi Augusto E. Bivona Salvatore Paterna Marta Valenza Renato Albiero

Biopsies of aortic tissue were obtained from patients undergoing heart surgery, and were tested for oestrogen binding sites. Tests were carried out using a 7 + 1-point dextran-coated charcoal method, and receptors were quantified both in the cytoplasmic and in the nuclear fractions using Scatchard plot analyses. Tests yielded positive results in 8 cases out of 13 (cytosol fraction) and in 10 cases out of 13 (nuclear fraction). Receptors showed high affinity for oestrogens, the Kd values ranging from 10(-11) M to 10(-10) M. These findings therefore suggest the occurrence of oestrogen receptors in human blood-vessels.

Scatchard plot

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In Vitro, In Vivo, and In Silico Studies of Cumanin Diacetate as a Potential Drug against Trypanosoma cruzi Infection

ACS Omega (2021)

Andrés Sánchez Alberti María Florencia Beer Natacha Cerny Augusto E. Bivona Lucas Fabián

The sesquiterpene lactones cumanin, helenalin, and hymenin and their semisynthetic derivatives were evaluated against Trypanosoma cruzi epimastigotes. The cytotoxicity of the compounds was evaluated on murine splenocytes. Cumanin diacetate was one of the most active and selective compounds [IC50 = 3.20 ± 0.52 μg/mL, selectivity index (SI) = 26.0]. This sesquiterpene lactone was selected for its evaluation on trypomastigote and amastigote forms of the parasite. The diacetylated derivative of cumanin showed moderate activity on trypomastigotes (IC50 = 32.4 ± 5.8 μg/mL). However, this compound was able to efficiently inhibit parasite replication with an IC50 value of 2.2 ± 0.05 μg/mL against the amastigote forms. Cumanin diacetate showed selectivity against the intracellular forms of Trypanosoma cruzi with an SI value of 52.7. This cumanin analogue was also active on an in vivo model of Chagas disease, leading to a reduction in the parasitemia levels in comparison with nontreated animals. Histopathological analysis of skeletal muscular tissues from treated mice showed only focal interstitial lymphocyte inflammatory infiltrates with slight myocyte necrosis; in contrast, nontreated animals showed severe lymphocyte inflammatory infiltrates with necrosis of the myocytes. A molecular docking study of cumanin and its derivatives on trypanothione reductase from T. cruzi (TcTR) was performed. The results of ΔG docking achieved let the identification of diacetylated and O-alkylated derivatives of cumanin as good inhibitors of TcTR. Cumanin diacetate could be considered a potential candidate for further studies for the development of new therapies against Chagas disease.

Amastigote

Chagas Disease

Sesquiterpene lactone

IC50

10.1021/acsomega.1c05560

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Citations (5)

Extracts and Terpenoids from Stevia Species as Potential Anthelmintics for Neglected Tropical Diseases Caused by Cestode Parasites

Molecules (2024)

María del Pilar Cevasco Contreras Jimena Borgo Ana M. Celentano Orlando G. Elso Hernán Gerónimo Bach

Cestodes are etiological agents of neglected diseases such as echinococcosis and cysticercosis, which are major public health problems. Antiparasitic treatment relies on a small number of approved drugs, which are often only partially effective, poorly tolerated and require prolonged administration. Thus, the discovery of novel potential treatments is critical. The

Neglected Tropical Diseases

Niclosamide

10.3390/molecules29184430

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