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

• Published in: Journal of controlled release 2015-09, Vol.214, p.12-22
• Main Authors: Sánchez Vallecillo, María F., Minguito de la Escalera, María M., Aguirre, María V., Ullio Gamboa, Gabriela V., Palma, Santiago D., González-Cintado, Leticia, Chiodetti, Ana L., Soldano, Germán, Morón, Gabriel, Allemandi, Daniel A., Ardavín, Carlos, Pistoresi-Palencia, María C., Maletto, Belkys A.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - chemistry; Animals; Antigens - administration & dosage; Ascorbic Acid - analogs & derivatives; Ascorbic Acid - chemistry; Ascorbyl palmitate; Controlled release; Danger-associated molecular patterns (DAMPs); Delayed-Action Preparations; Humans; Inflammasomes - drug effects; Inflammation - chemically induced; Inflammation - pathology; Interleukins - biosynthesis; Leukocytes - drug effects; Liquid crystal; Liquid Crystals; Mice; Mice, Knockout; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Nanostructure; Ovalbumin - immunology; Toll-Like Receptor 9 - biosynthesis; Toll-Like Receptor 9 - genetics; Toll-Like Receptors - biosynthesis; Vaccine adjuvant; Vaccines - administration & dosage
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2015.07.008

Modern subunit vaccines require the development of new adjuvant strategies. Recently, we showed that CpG-ODN formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate (Coa-ASC16) is an attractive system for promoting an antigen-specific immune response to weak antigens. Here, we showed 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 dye-OVA 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 the whole 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 TLR9-deficient mice 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 pro-inflammatory activity. Understanding how Coa-ASC16 works might have significant implications for rational vaccine design. [Display omitted]