INVESTIGADORES
PALMA Santiago Daniel
artículos
Título:
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
Autor/es:
SANCHEZ VALLECILLO, MARIA FERNANDA; MINGUITO DE LA ESCALERA, MARIA; AGUIRRE VIRGINIA; GABRIELA ULLIO GAMBOA,; PALMA S. D; GOZALEZ-CINTADO LETICIA; CHIODETTI A; SODANO GERMAN; MORON GABRIEL; ALLEMANDI D,; ARDAVIN CARLOS; PISTORESI M. C.; MALETTO, B
Revista:
JOURNAL OF CONTROLLED RELEASE
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2015 vol. 214 p. 12 - 22
ISSN:
0168-3659
Resumen:
Modern subunit vaccines require the development of new adjuvant strategies. Recently, we showed that CpGODN formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate (CoaASC16) is an attractive system for promoting an antigen-specific immune response to weak antigens. Here, weshowed that after subcutaneous injection of mice with near-infrared fluorescent dye-labeled OVA antigen formulated with Coa-ASC16, the dye-OVA was retained at the injection site for a longer period than when soluble dyeOVA was administered. Coa-ASC16 alone elicited a local inflammation, but how this material triggers this response has not been described yet. Although it is known that some materials used as a platform are not immunologically inert, very few studies have directly focused on this topic. In this study, we explored the underlying mechanisms concerning the interaction between Coa-ASC16 and the immune system and we found that thewhole inflammatory response elicited by Coa-ASC16 (leukocyte recruitment and IL-1β, IL-6 and IL-12 production) was dependent on the MyD88 protein. TLR2, TLR4, TLR7 and NLRP3-inflammasome signaling were not required for induction of this inflammatory response. Coa-ASC16 induced local release of self-DNA, and in TLR9deficientmice IL-6 production was absent. In addition, Coa-ASC16 revealed an intrinsic adjuvant activity which was affected by MyD88 and IL-6 absence. Taken together these results indicate that Coa-ASC16 used as a vaccine platform is effective due to the combination of the controlled release of antigen and its intrinsic proinflammatoryactivity. Understanding how Coa-ASC16 works might have significant implications for rational vaccine design.