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Artículo

Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease

Bontempi, IvánIcon ; Vicco, Miguel HernánIcon ; Cabrera, Gabriel GustavoIcon ; Villar, Silvina RaquelIcon ; González, Florencia BelénIcon ; Roggero, Eduardo Angel; Ameloot, Paul; Callewaert, Nico; Perez, Ana RosaIcon ; Marcipar, Ivan SergioIcon
Fecha de publicación: 03/2015
Editorial: Elsevier
Revista: Vaccine
ISSN: 0264-410X
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Tecnologías que involucran la identificación de ADN, proteínas y enzimas, y cómo influyen en el conjunto de enfermedades y mantenimiento del bienestar

Resumen

Recombinant protein vaccines are safe but elicit low immunological responses. The new generation of adjuvants is currently reversing this situation. Here, a new antigen–adjuvant combination for protection against experimental Chagas disease was assessed. The antigen used in the formulation was a glycosylated mutant inactive trans-sialidase (mTS) that was previously proven to be highly protective against Trypanosoma cruzi infection; here, we show that it can be produced in large quantities and high quality using Pichia pastoris. The adjuvant used in the formulation was ISCOMATRIX (IMX), which was found to be effective and safe in human clinical trials of vaccines designed to control other intracellular infections. Fifteen days after the third immunization, mice immunized with mTS-IMX showed a TS-specific IgG response with titers >106 and high avidity, an increased IgG2a/IgG1 ratio, significant delayed-type hypersensitivity (DTH) reactivity, a balanced production of IFN-γ and IL-10 by splenocytes and a strong IFN-γ secretion by CD8+ T lymphocytes. When these mice where challenged with 1000 trypomastigotes of T. cruzi, all mTS-IMX immunized mice survived, whereas mice immunized with mTS alone, IMX or PBS exhibited high mortality. Remarkably, during acute infection, when the parasitemia is highest in this infection model (day 21), mTS-IMX immunized mice had ∼50 times less parasitemia than non-immunized mice. At this moment and also in the chronic phase, 100 days after infection, tissue presented ∼4.5 times lower parasite load and associated inflammatory infiltrate and lesions. These results indicate that protection against Chagas disease can be achieved by a protein antigen–adjuvant mTS formulation that is compatible with human medicine. Therefore, the current formulation is a highly promising T. cruzi vaccine candidate to be tested in clinical trials.
Palabras clave: Trypanosoma Cruzi , Iscom , Trans-Sialidase , Vaccine
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/13440
DOI: http://dx.doi.org/10.1016/j.vaccine.2015.01.044
URL: http://www.sciencedirect.com/science/article/pii/S0264410X15000882
Colecciones
Articulos(CCT - ROSARIO)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Articulos(CCT - SANTA FE)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SANTA FE
Citación
Bontempi, Iván; Vicco, Miguel Hernán; Cabrera, Gabriel Gustavo; Villar, Silvina Raquel; González, Florencia Belén; et al.; Efficacy of a trans-sialidase-ISCOMATRIX subunit vaccine candidate to protect against experimental Chagas disease; Elsevier; Vaccine; 33; 10; 3-2015; 1274-1283
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