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Artículo

Oral co-administration of a bacterial protease inhibitor in the vaccine formulation increases antigen delivery at the intestinal epithelial barrier

Coria, Mirta LorenaIcon ; Risso, Gabriela SofíaIcon ; Guaimas, Francisco FernandoIcon ; Ferrero, Mariana CristinaIcon ; Bruno, Laura; Pasquevich, Karina AlejandraIcon ; Cassataro, JulianaIcon
Fecha de publicación: 01/2019
Editorial: Elsevier Science
Revista: Journal of Controlled Release
ISSN: 0168-3659
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Inmunología

Resumen

The study of capture and processing of antigens (Ags) by intestinal epithelial cells is very important for development of new oral administration systems. Efficient oral Ag delivery systems must resist enzymatic degradation by gastric and intestinal proteases and deliver the Ag across biological barriers. The recombinant unlipidated outer membrane protein from Brucella spp. (U-Omp19) is a protease inhibitor with immunostimulatory properties used as adjuvant in oral vaccine formulations. In the present work we further characterized its mechanism of action and studied the interaction and effect of U-Omp19 on the intestinal epithelium. We found that U-Omp19 inhibited protease activity from murine intestinal brush-border membranes and cysteine proteases from human intestinal epithelial cells (IECs) promoting co-administered Ag accumulation within lysosomal compartments of IECs. In addition, we have shown that co-administration of U-Omp19 facilitated the transcellular passage of Ag through epithelial cell monolayers in vitro and in vivo while did not affect epithelial cell barrier permeability. Finally, oral co-delivery of U-Omp19 in mice induced the production of Ag-specific IgA in feces and the increment of CD103+ CD11b− CD8α+ dendritic cells subset at Peyer's patches. Taken together, these data describe a new mechanism of action of a mucosal adjuvant and support the use of this rationale/strategy in new oral delivery systems for vaccines.
Palabras clave: BACTERIAL PROTEASE INHIBITOR , ENTEROCYTES , INTESTINAL BARRIER , ORAL DELIVERY , VACCINE ADJUVANT
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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 2.5 Unported (CC BY 2.5)
Identificadores
URI: http://hdl.handle.net/11336/132725
URL: https://linkinghub.elsevier.com/retrieve/pii/S0168365918306862
DOI: http://dx.doi.org/10.1016/j.jconrel.2018.11.025
Colecciones
Articulos (IIBIO)
Articulos de INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS
Articulos(IDEHU)
Articulos de INST.DE EST.DE LA INMUNIDAD HUMORAL PROF.R.A.MARGNI
Citación
Coria, Mirta Lorena; Risso, Gabriela Sofía; Guaimas, Francisco Fernando; Ferrero, Mariana Cristina; Bruno, Laura; et al.; Oral co-administration of a bacterial protease inhibitor in the vaccine formulation increases antigen delivery at the intestinal epithelial barrier; Elsevier Science; Journal of Controlled Release; 293; 1-2019; 158-171
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