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13 results on '"Iván, Marcipar"'

1. Improved serodiagnosis of Trypanosoma vivax infections in cattle reveals high infection rates in the livestock regions of Argentina.

Author

Iván Alejandro Bontempi, Diego Gustavo Arias, Graciela Verónica Castro, Luz María Peverengo, Genaro Francisco Díaz, Martín Allassia, Gonzalo Greif, and Iván Marcipar

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

Bovine trypanosomosis, caused by Trypanosoma vivax, currently affects cattle and has a significant economic impact in sub-Saharan Africa and South America. The development of new diagnostic antigens is essential to improve and refine existing methods. Our study evaluated the efficacy of two recombinant antigens in detecting specific antibodies in cattle. These antigens are derivatives of an invariant surface glycoprotein (ISG) from T. vivax. A fraction of a previously described antigen (TvY486_0045500), designated TvISGAf, from an African strain was evaluated, and a new ISG antigen from an American isolate, TvISGAm, was identified. The two antigens were expressed as fusion proteins in Escherichia coli: TvISGAf was fused to the MBP-His-tag, and TvISGAm was obtained as a His-tag fused protein. An ELISA evaluation was conducted using these antigens on 149 positive and 63 negative bovine samples. The diagnostic performance was enhanced by the use of a combination of both antigens (referred to as TvISG-based ELISA), achieving a sensitivity of 89.6% and specificity of 93.8%. Following the validation of the TvISG-based ELISA, the seroprevalence of T. vivax infection in 892 field samples from cattle in the central region of Argentina was determined. The mean seroprevalence of T. vivax was 53%, with variation ranging from 21% to 69% among the six departments studied. These results support the use of the TvISG ELISA as a valuable serological tool for the detection and monitoring of T. vivax infection in cattle. Furthermore, we report for the first time the seroprevalence of T. vivax in Argentina, which highlights the widespread endemic nature of the disease in the region. In order to effectively manage the increasing spread of T. vivax in the vast livestock production areas of South America, it is essential to implement consistent surveillance programs and to adopt preventive strategies.

Published
2024
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2. Intranasal Trans-Sialidase Vaccine Mitigates Acute and Chronic Pathology in a Preclinical Oral Chagas Disease Model

Author

Maria Florencia Pacini, Camila Bulfoni Balbi, Brenda Dinatale, Cecilia Farré, Paula Cacik, Florencia Belén Gonzalez, Iván Marcipar, and Ana Rosa Pérez

Subjects
oral Chagas disease, chronic Chagas cardiomyopathy, Trypanosoma cruzi, trans-sialidase, nasal vaccine, c-di-AMP, Medicine
Abstract

Chagas disease, caused by Trypanosoma cruzi, leads to severe complications in 30% of infected individuals, including acute myocarditis and chronic fibrosing cardiomyopathy. Despite the significant burden of this disease, there is currently no licensed vaccine available to prevent it. This study aimed to evaluate the mucosal and systemic immunogenicity as well as the prophylactic efficacy of a mucosal vaccine candidate and its impact on both acute and chronic cardiomyopathy. The results showed that the nasal administration of trans-sialidase (TS) plus c-di-AMP (TS+A) vaccine elicited a NALT expression of IFN-γ, IL-17a and IL-4 mRNA as well as a nasal-specific production of IgA. An in vivo challenge with TS also triggered increased proliferation of lymphocytes from the NALT, sentinel cervical lymph node, and spleen. TS+A immunization increased the plasma levels of Th1/Th2/Th17 cytokines and elicited an evident cellular response by which to judge enhanced delayed-type hypersensitivity responses following a TS footpad challenge. After oral infection, TS+A-vaccinated mice showed significantly reduced parasitemia and parasite load in the heart, muscles and intestines, while markers of hepatic and muscle damage as well as clinical manifestations of acute infection were strongly diminished. TS+A also attenuated acute myocarditis and the expression of inflammatory markers in the heart. The protection conferred by TS+A extended into the chronic phase, where it resulted in a clear reduction in chronic myocarditis, fibrosis and functional electrocardiographic abnormalities, associated with a decreased expression of the pro-fibrotic TGF-β. These results revealed that it is possible to develop a mucosal vaccine against T. cruzi based on TS and c-di-AMP that is capable of reducing the development of Chagas cardiomyopathy, the hallmark of Chagas disease.

Published
2024
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3. Targeting Myeloid-Derived Suppressor Cells to Enhance a Trans-Sialidase-Based Vaccine Against Trypanosoma cruzi

Author

Juan Cruz Gamba, Carolina Roldán, Estefanía Prochetto, Giuliana Lupi, Iván Bontempi, Carolina Verónica Poncini, Mónica Vermeulen, Ana Rosa Pérez, Iván Marcipar, and Gabriel Cabrera

Subjects
Trypanosoma cruzi, myeloid derived suppressor cells, vaccine, trans-sialidase, adjuvant, Microbiology, QR1-502
Abstract

Trypanosoma cruzi (T. cruzi) is a hemoflagellate protozoan parasite that causes Chagas disease, a neglected tropical disease that affects more than 6 million people around the world, mostly in Latin America. Despite intensive research, there is no vaccine available; therefore, new approaches are needed to further improve vaccine efficacy. It is well established that experimental T. cruzi infection induces a marked immunosuppressed state, which includes notably increases of CD11b+ GR-1+ myeloid-derived suppressor cells (MDSCs) in the spleen, liver and heart of infected mice. We previously showed that a trans-sialidase based vaccine (TSf-ISPA) is able to confer protection against a virulent T. cruzi strain, stimulating the effector immune response and decreasing CD11b+ GR-1+ splenocytes significantly. Here, we show that even in the immunological context elicited by the TSf-ISPA vaccine, the remaining MDSCs are still able to influence several immune populations. Depletion of MDSCs with 5 fluorouracil (5FU) at day 15 post-infection notably reshaped the immune response, as evidenced by flow cytometry of spleen cells obtained from mice after 21 days post-infection. After infection, TSf-ISPA-vaccinated and 5FU-treated mice showed a marked increase of the CD8 response, which included an increased expression of CD107a and CD44 markers in CD8+ cultured splenocytes. In addition, vaccinated and MDSC depleted mice showed an increase in the percentage and number of CD4+ Foxp3+ regulatory T cells (Tregs) as well as in the expression of Foxp3+ in CD4+ splenocytes. Furthermore, depletion of MDSCs also caused changes in the percentage and number of CD11chigh CD8α+ dendritic cells as well as in activation/maturation markers such as CD80, CD40 and MHCII. Thus, the obtained results suggest that MDSCs not only play a role suppressing the effector response during T. cruzi infection, but also strongly modulate the immune response in vaccinated mice, even when the vaccine formulation has a significant protective capacity. Although MDSC depletion at day 15 post-infection did not ameliorated survival or parasitemia levels, depletion of MDSCs during the first week of infection caused a beneficial trend in parasitemia and mice survival of vaccinated mice, supporting the possibility to target MDSCs from different approaches to enhance vaccine efficacy. Finally, since we previously showed that TSf-ISPA immunization causes a slight but significant increase of CD11b+ GR-1+ splenocytes, here we also targeted those cells at the stage of immunization, prior to T. cruzi challenge. Notably, 5FU administration before each dose of TSf-ISPA vaccine was able to significantly ameliorate survival and decrease parasitemia levels of TSf-ISPA-vaccinated and infected mice. Overall, this work supports that targeting MDSCs may be a valuable tool during vaccine design against T. cruzi, and likely for other pathologies that are characterized by the subversion of the immune system.

Published
2021
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4. Intranasal Trans-sialidase-based vaccine against Trypanosoma cruzi triggers a mixed cytokine profile in the nasopharynx-associated lymphoid tissue and confers local and systemic immunogenicity

Author

Pacini, María F., primary, Camila, Bulfoni Balbi, additional, Brenda, Dinatale, additional, González, Florencia B., additional, Estefania, Prochetto, additional, de Hernández, María A., additional, Pamela, Cribb, additional, Cecilia, Farré, additional, Martín, Espariz, additional, Blancato, Víctor S., additional, Christian, Magni, additional, Iván, Marcipar, additional, and Pérez, Ana R., additional

Published
2023
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5. Nasal immunization with a L. lactis-derived trans-sialidase antigen plus c-di-AMP protects against acute oral T. cruzi infection

Author

Maria Florencia, Pacini, Florencia Belén, González, Brenda, Dinatale, Camila, Bulfoni Balbi, Silvina Raquel, Villar, Cecilia, Farré, Giuliana, Lupi, Martín, Espariz, Víctor Sebastián, Blancato, Christian, Magni, Iván, Marcipar, and Ana Rosa, Pérez

Subjects
Protozoan Vaccines, Mice, Inbred BALB C, General Veterinary, General Immunology and Microbiology, Trypanosoma cruzi, Public Health, Environmental and Occupational Health, Neuraminidase, Mice, Infectious Diseases, Animals, Molecular Medicine, Chagas Disease, Immunization, Dinucleoside Phosphates, Glycoproteins
Abstract

The new generation of vaccines for Chagas disease, are focused to induce both humoral and cellular response to effectively control Trypanosoma cruzi parasites. The administration of vaccine formulations intranasally has the advantage over parenteral routes that can induce a specific response at mucosal and systemic levels. This study aimed to evaluate and compare the immunogenicity and prophylactic effectiveness of two Trans-sialidase (TS)-based mucosal vaccines against T. cruzi administered intranasally. Vaccines consisted of a recombinant fragment of TS expressed in Lactococcus lactis formulated in two different adjuvants. The first, was an immunostimulant particle (ISPA, an ISCOMATRIX-like adjuvant), while the second was the dinucleotide c-di-AMP, which have shown immunostimulant properties at the mucosal level. BALB/c mice were immunized intranasally (3 doses, one every two weeks) with each formulation (TS + ISPA or TS + c-di-AMP) and with TS alone or vehicle (saline solution) as controls. Fifteen days after the last immunization, both TS + ISPA or TS + c-di-AMP induced an evident systemic humoral and cellular response, as judged by the increased plasma anti-TS IgG2a titers and IgG2a/IgG1 ratio and enhanced cellular response against TS. Plasma derived antibodies from TS + c-di-AMP also inhibit in vitro the invasion capacity of T. cruzi. Furthermore, specific secretory IgA was more enhanced in TS + c-di-AMP group. Protective efficacy was proved in vaccinated animals by an oral T. cruzi-challenge. Parasitemia control was only achieved by animals vaccinated with TS + c-di-AMP, despite all vaccinates groups showed enhanced CD8

Published
2022

7. Genetic Engineering of Lactococcus lactis Co-producing Antigen and the Mucosal Adjuvant 3′ 5′- cyclic di Adenosine Monophosphate (c-di-AMP) as a Design Strategy to Develop a Mucosal Vaccine Prototype

Author

Ingrid Quintana, Martín Espariz, Silvina R. Villar, Florencia B. González, Maria F. Pacini, Gabriel Cabrera, Iván Bontempi, Estefanía Prochetto, Jörg Stülke, Ana R. Perez, Iván Marcipar, Victor Blancato, and Christian Magni

Subjects
Lactococcus lactis, c-di-AMP adjuvant, live vaccine, delivery system, T. cruzi, trans-sialidase, Microbiology, QR1-502
Abstract

Lactococcus lactis is a promising candidate for the development of mucosal vaccines. More than 20 years of experimental research supports this immunization approach. In addition, 3′ 5′- cyclic di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger that plays a key role in the regulation of diverse physiological functions (potassium and cellular wall homeostasis, among others). Moreover, recent studies showed that c-di-AMP has a strong mucosal adjuvant activity that promotes both humoral and cellular immune responses. In this study, we report the development of a novel mucosal vaccine prototype based on a genetically engineered L. lactis strain. First, we demonstrate that homologous expression of cdaA gen in L. lactis is able to increase c-di-AMP levels. Thus, we hypothesized that in vivo synthesis of the adjuvant can be combined with production of an antigen of interest in a separate form or jointly in the same strain. Therefore, a specifically designed fragment of the trans-sialidase (TScf) enzyme from the Trypanosoma cruzi parasite, the etiological agent of Chagas disease, was selected to evaluate as proof of concept the immune response triggered by our vaccine prototypes. Consequently, we found that oral administration of a L. lactis strain expressing antigenic TScf combined with another L. lactis strain producing the adjuvant c-di-AMP could elicit a TS-specific immune response. Also, an additional L. lactis strain containing a single plasmid with both cdaA and tscf genes under the Pcit and Pnis promoters, respectively, was also able to elicit a specific immune response. Thus, the current report is the first one to describe an engineered L. lactis strain that simultaneously synthesizes the adjuvant c-di-AMP as well as a heterologous antigen in order to develop a simple and economical system for the formulation of vaccine prototypes using a food grade lactic acid bacterium.

Published
2018
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8. Intranasal trans-sialidase-based vaccine against Trypanosoma cruzi triggers a mixed cytokine profile in the nasopharynx-associated lymphoid tissue and confers local and systemic immunogenicity

Author

María F. Pacini, Camila Bulfoni Balbi, Brenda Dinatale, Florencia B. González, Estefania Prochetto, María A. De Hernández, Pamela Cribb, Cecilia Farré, Martín Espariz, Víctor S. Blancato, Christian Magni, Iván Marcipar, and Ana R. Pérez

Subjects
Infectious Diseases, Insect Science, Veterinary (miscellaneous), Parasitology
Published
2023

9. Development of low-cost cage-like particles to formulate veterinary vaccines

Author

Giuliana A. Lupi, Florencia X. Santiago Valtierra, Gabriel Cabrera, Roque Spinelli, Álvaro S. Siano, Verónica González, Antonio Osuna, Gerardo M. Oresti, and Iván Marcipar

Subjects
Mice, Vaccines, Adjuvants, Immunologic, General Veterinary, Ovalbumin, Immunoglobulin G, Immunology, Animals, Saponins
Abstract

Low-cost adjuvants are urgently needed for the development of veterinary vaccines able to trigger strong immune responses. In this work, we describe a method to obtain a low-cost cage-like particles (ISCOMATRIX-like) adjuvant useful to formulate veterinary vaccines candidates. The main components to form the particles are lipids and saponins, which were obtained from egg yolk by ethanolic extraction and by dialyzing a non-refined saponins extract, respectively. Lipids were fully characterized by thin layer chromatography (TLC) and gas-chromatography (GC) and enzymatic methods, and saponins were characterized by TLC, HPLC and MALDI-TOF. Cage-like particles were prepared with these components or with commercial inputs. Both particles and the traditional Alum used in veterinary vaccines were compared by immunizing mice with Ovalbumin (OVA) formulated with these adjuvants and assessing IgG1, IgG2a anti OVA antibodies and specific Delayed-type Hypersensitivity (DTH). In the yolk extract, a mixture of phospholipids, cholesterol and minor components of the extract (e.g. lyso-phospholipids) with suitable proportions to generate cage-like particles was obtained. Also, semi-purified saponins with similar features to those of the QuilA® were obtained. Cage-like particles prepared with these components have 40-50 nm and triggers similar levels of Anti-OVA IgG1 and DTH than with commercial inputs but higher specific-IgG2a. Both adjuvants largely increased the levels of IgG1, IgG2a and DTH in relation to the formulation with Alum. The methods described to extract lipids from egg yolk and saponins from non-refined extract allowed us to obtain an inexpensive and highly effective adjuvant.

Published
2022

10. Assessment of a combined treatment with a therapeutic vaccine and benznidazole for the Trypanosoma cruzi chronic infection

Author

Estefanía, Prochetto, Iván, Bontempi, Luz, Rodeles, Gabriel, Cabrera, Miguel, Vicco, Paula, Cacik, María Florencia, Pacini, Mónica, Pérez Gianeselli, Ana Rosa, Pérez, and Iván, Marcipar

Subjects
Mice, Vaccines, Infectious Diseases, Nitroimidazoles, Trypanosoma cruzi, Insect Science, Veterinary (miscellaneous), Animals, Chagas Disease, Persistent Infection, Parasitology, Trypanocidal Agents
Abstract

The difficulties encountered in achieving treatments for chronic Chagas disease have promoted the investigation of new therapeutic strategies. In this study, we used two murine models of Trypanosoma cruzi chronic infection to determine the usefulness of applying a therapeutic vaccine alone or followed by benznidazole (Bz) chemotherapy. A vaccine formulation based on an N-terminal fragment of Trans-sialidase (TS) and Immunostimulant Particle Adjuvant (ISPA) - TSNt-ISPA was obtained. Firstly, the immunogenicity and protective capacity of TSNt-ISPA was demonstrated as a prophylactic formulation in an acute model of infection. Later, the formulation was assessed as a therapeutic vaccine alone or combined with (Bz) using two models of chronic infection. BALB/c mice chronically infected with Sylvio X10/4 or Tulahuen cl2 T. cruzi strains were not treated as control or treated only with the therapeutic vaccine TSNt-ISPA, with a combined treatment TSNt-ISPA+Bz (Bz applied after the vaccine), or only with Bz. The vaccination schedule consisted of TSNt-ISPA administration at days110, 120, and 130 post-infection (pi) and Bz administration was performed daily from day 140 to 170 pi. At day 273 pi, electrocardiographic (ECG) parameters, heart parasite load, myocarditis, and heart fibrosis were assessed. In both models, therapeutic administration of TSNt-ISPA reduced ECG alterations and the cardiac tissue damage observed in the chronic phase. Moreover, vaccine treatment significantly decreased heart parasite load in both Sylvio X10/4 and Tulahuen cl2 infected mice. The combined treatment, but not Bz or vaccine administration alone, allowed to restore ECG parameters in Tulahuen cl2 infected mice. The results indicate the usefulness of the therapeutic TSNt-ISPA formulation in BALB/c mice chronically infected with Sylvio X10/4 or Tulahuen cl2 strain. For the mice infected with T. cruzi Tulahuen cl2 strain, the combined treatment with the vaccine and Bz had a more positive effect on the course of heart disease than the individual treatments with the vaccine or Bz alone.

Published
2022

11. Film Forming Nanogels for Needle‐Free Transdermal Vaccination

Author

Ana Sonzogni, Gabriel Cabrera, Giuliana Lupi, Luis Gugliotta, Verónica Gonzalez, Iván Marcipar, and Roque Minari

Subjects
Biomaterials, Polymers and Plastics, Vaccination, Materials Chemistry, Nanogels, Immunization, Bioengineering, Antigens, Administration, Cutaneous, Skin, Biotechnology
Abstract

Transcutaneous immunization (TCI) provides a valuable alternative approach to conventional vaccination because of the high accessibility and the exceptional immunological characteristics of the skin, but its application is limited by the low permeability of the stratum corneum. Although nanogels (NGs) have proven to enhance skin penetration of macromolecules with minimum damage, their use in TCI remains almost unexplored. In this context, this article evaluates the performance of novel film-forming NGs (FF-NGs) as TCI. This TCI platform consists of NGs with multilobular morphology that positively combines the properties of cross-linked poly(N-vinylcaprolactam), like thermoresponsiveness and the ability to load and release a cargo, with the film-forming capacity of low Tg lobes. FF-NGs and formed films are characterized at different levels. Formed films show to be able to uniformly load an antigenic protein and release it with a profile depending on the temperature and on their FF-NGs content. In vivo studies have demonstrated that FF-NGs promote the penetration of not only an antigenic protein, but also an adjuvant until the immunocompetent area of skin, generating an adjuvant-dependent specific immune response. Finally, this study provides a successful proof of concept that FF-NGs can be a powerful tool for the transcutaneous release of complex formulations.

Published
2022

12. Genetic Engineering of

Author

Ingrid, Quintana, Martín, Espariz, Silvina R, Villar, Florencia B, González, Maria F, Pacini, Gabriel, Cabrera, Iván, Bontempi, Estefanía, Prochetto, Jörg, Stülke, Ana R, Perez, Iván, Marcipar, Victor, Blancato, and Christian, Magni

Published
2018

13. Humoral immune response against P2β from Trypanosoma cruzi in persons with chronic chagas disease: Its relationship with treatment against parasites and myocardial damage

Author

Diana L, Fabbro, Verónica, Olivera, Maria Laura, Bizai, Susana, Denner, Cristina, Diez, Iván, Marcipar, Iván, Mancipar, Mirtha, Streiger, Enrique, Arias, Mónica, del Barco, Diego, Mendicino, and Oscar, Bottasso

Subjects
Chagas disease, Male, Ribosomal Proteins, CIENCIAS MÉDICAS Y DE LA SALUD, Humoral Immune Response, Trypanosoma cruzi, Protozoan Proteins, Antibodies, Protozoan, Ciencias de la Salud, Biology, Asymptomatic, Group A, Group B, Virology, medicine, Animals, Humans, Chagas Disease, Nifurtimox, Articles, biology.organism_classification, medicine.disease, Trypanocidal Agents, Immunity, Humoral, Treatment, Enfermedades Infecciosas, Chronic infection, Infectious Diseases, Nitroimidazoles, Immunology, Chronic Disease, biology.protein, Parasitology, Female, Myocardial Damage, medicine.symptom, Antibody, Cardiomyopathies, medicine.drug
Abstract

We investigated the relationship between potentially pathogenic antibodies against a Trypanosoma cruzi ribosomal protein (P2β) and the evolution of Chagas disease and the effect of trypanocidal treatment on these variables. Seventy-eight patients with chronic Chagas disease who were followed-up for more than 20 years were divided into three groups: 30 asymptomatic persons undergoing specific treatment (group A), 37 asymptomatic persons not undergoing specific treatment (group B), and 11 patients with chronic chagasic cardiomyopathy (CCC) who were not treated. Five patients in group B showed evolution to myocardial abnormalities. Among persons with CCC, six showed no changes; the remaining persons showed progression of cardiac involvement. Levels of antibodies to P2β in persons in group A decreased from their initial values. This finding was not observed in persons in groups B and C. Comparisons at the end of the follow-up showed lower amounts of antibodies to P2β in groups A and C. These findings support the benefits of specific treatment during chronic infection. Fil: Fabbro, Diana Lucrecia. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Centro de Invest.sobre Endemias Nacionales; Argentina Fil: Olivera, Veronica Soledad. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Centro de Invest.sobre Endemias Nacionales; Argentina Fil: Bizai, María Laura. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Centro de Invest.sobre Endemias Nacionales; Argentina Fil: Denner, Susana. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Centro de Invest.sobre Endemias Nacionales; Argentina Fil: Diez, Cristina Noemí. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Centro de Invest.sobre Endemias Nacionales; Argentina Fil: Marcipar, Iván Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Centro de Invest.sobre Endemias Nacionales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina Fil: Streiger, Mirtha. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Centro de Invest.sobre Endemias Nacionales; Argentina Fil: Arias, Enrique. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Centro de Invest.sobre Endemias Nacionales; Argentina Fil: del Barco, Mónica. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Centro de Invest.sobre Endemias Nacionales; Argentina Fil: Mendicino, Diego. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Centro de Invest.sobre Endemias Nacionales; Argentina Fil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Centro de Invest.sobre Endemias Nacionales; Argentina

Published
2011

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