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Artículo

Class-B CpG-ODN formulated with a nanostructure induces type I interferons-dependent and CD4+T cell-independent CD8+T-Cell response against unconjugated protein antigen

Chiodetti, Ana LauraIcon ; Sánchez Vallecillo, María FernandaIcon ; Dolina, Joseph S.; Crespo, Maria InesIcon ; Marin, Constanza; Schoenberger, Stephen P.; Allemandi, Daniel AlbertoIcon ; Palma, Santiago DanielIcon ; Pistoresi, Maria CristinaIcon ; Moron, Victor GabrielIcon ; Maletto, Belkys AngélicaIcon
Fecha de publicación: 10/2018
Editorial: Frontiers Media S.A.
Revista: Frontiers in Immunology
ISSN: 1664-3224
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Inmunología

Resumen

There is a need for new vaccine adjuvant strategies that offer both vigorous antibody and T-cell mediated protection to combat difficult intracellular pathogens and cancer. To this aim, we formulated class-B synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) with a nanostructure (Coa-ASC16 or coagel) formed by self-assembly of 6-0-ascorbyl palmitate ester. Our previous results demonstrated that mice immunized with ovalbumin (OVA) and CpG-ODN formulated with Coa-ASC16 (OVA/CpG-ODN/Coa-ASC16) elicited strong antibodies (IgG1 and IgG2a) and Th1/Th17 cellular responses without toxic systemic effects. These responses were superior to those induced by a solution of OVA with CpG-ODN or OVA/CpG-ODN formulated with aluminum salts. In this study, we investigated the capacity of this adjuvant strategy (CpG-ODN/Coa-ASC16) to elicit CD8+ T-cell response and some of the underlying cellular and molecular mechanisms involved in adaptive response. We also analyzed whether this adjuvant strategy allows a switch from an immunization scheme of three-doses to one of single-dose. Our results demonstrated that vaccination with OVA/CpG-ODN/Coa-ASC16 elicited an antigen-specific long-lasting humoral response and importantly-high quality CD8+ T-cell immunity with a single-dose immunization. Moreover, Coa-ASC16 promoted co-uptake of OVA and CpG-ODN by dendritic cells. The CD8+ T-cell response induced by OVA/CpG-ODN/Coa-ASC16 was dependent of type I interferons and independent of CD4+ T-cells, and showed polyfunctionality and efficiency against an intracellular pathogen. Furthermore, the cellular and humoral responses elicited by the nanostructured formulation were IL-6-independent. This system provides a simple and inexpensive adjuvant strategy with great potential for future rationally designed vaccines.
Palabras clave: ADJUVANT , ASCORBYL PALMITATE ESTER , CD8+ T-CELL RESPONSE , CPG-ODN , NANOSTRUCTURE , TYPE I INTERFERONS , 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 2.5 Unported (CC BY 2.5)
Identificadores
URI: http://hdl.handle.net/11336/95888
URL: https://www.frontiersin.org/article/10.3389/fimmu.2018.02319/full
DOI: https://doi.org/10.3389/fimmu.2018.02319
Colecciones
Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos(UNITEFA)
Articulos de UNIDAD DE INVESTIGACION Y DESARROLLO EN TECNOLOGIA FARMACEUTICA
Citación
Chiodetti, Ana Laura; Sánchez Vallecillo, María Fernanda; Dolina, Joseph S.; Crespo, Maria Ines; Marin, Constanza; et al.; Class-B CpG-ODN formulated with a nanostructure induces type I interferons-dependent and CD4+T cell-independent CD8+T-Cell response against unconjugated protein antigen; Frontiers Media S.A.; Frontiers in Immunology; 9; 10-2018; 1-14
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