Artículos de revistas
A liquid crystal of ascorbyl palmitate, used as vaccine platform, provides sustained release of antigen and has intrinsic pro-inflammatory and adjuvant activities which are dependent on MyD88 adaptor protein
Fecha
2015-09-28Registro en:
Sánchez Vallecillo, María Fernanda; Minguito de la Escalera, María; Aguirre, María Virginia; Ullio Gamboa, Gabriela Veronica; Palma, Santiago Daniel; et al.; A liquid crystal of ascorbyl palmitate, used as vaccine platform, provides sustained release of antigen and has intrinsic pro-inflammatory and adjuvant activities which are dependent on MyD88 adaptor protein; Elsevier Science; Journal of Controlled Release; 214; 28-9-2015; 12-22
0168-3659
1873-4995
CONICET Digital
CONICET
Autor
Sánchez Vallecillo, María Fernanda
Minguito de la Escalera, María
Aguirre, María Virginia
Ullio Gamboa, Gabriela Veronica
Palma, Santiago Daniel
Gonzalez Cintado, Leticia
Chiodetti, Ana Laura
Soldano, Germán
Moron, Victor Gabriel
Allemandi, Daniel Alberto
Ardavín, Carlos
Pistoresi, Maria Cristina
Maletto, Belkys Angélica
Resumen
Modern subunit vaccines require the development of new adjuvant strategies. Recently,32 we showed that CpG-ODN formulated with a liquid crystal nanostructure formed by self33assembly of 6-O-ascorbyl palmitate (Coa-ASC16) is an attractive system for promoting an34 antigen-specific immune response to weak antigens. Here, we showed that after35 subcutaneous injection of mice with near-infrared fluorescent dye-labeled OVA antigen36 formulated with Coa-ASC16, the dye-OVA was retained at the injection site for a longer37 period than when soluble dye-OVA was administered. Coa-ASC16 alone elicited a local38 inflammation, but how this material triggers this response has not been described yet.39 Although it is known that some materials used as a platform are not immunologically inert,40 very few studies have directly focused on this topic. In this study, we explored the41 underlying mechanisms concerning the interaction between Coa-ASC16 and the immune42 system and we found that the whole inflammatory response elicited by Coa-ASC1643 (leukocyte recruitment and IL-1β, IL-6 and IL-12 production) was dependent on the MyD8844 protein. TLR2, TLR4, TLR7 and NLRP3-inflammasome signaling were not required for45 induction of this inflammatory response. Coa-ASC16 induced local release of self-DNA,46 and in TLR9-deficient mice IL-6 production was absent. In addition, Coa-ASC16 revealed47 an intrinsic adjuvant activity which was affected by MyD88 and IL-6 absence. Taken48 together these results indicate that Coa-ASC16 used as a vaccine platform is effective due49 to the combination of the controlled release of antigen and its intrinsic pro-inflammatory50 activity. Understanding how Coa-ASC16 works might have significant implications for51 rational vaccine design.