A nanostructure from ascorbyl palmitate based-adjuvant boosts adaptive immunity by inducing an inflammatory effect at the injection site, both properties require the adaptor protein Myd88.

SANCHEZ-VALLECILLO,MF; ULLO, G; PALMA, S; GONZÁLEZ-CINTADO,L; CHIODETTI, A; AGUIRRE,MV; MORÓN, G; ARDAVIN,C; PISTORESI, MC; MALETTO, B

Mar del Plata

Congreso; LXII Reunión de la Sociedad Argentina de Inmunología.; 2014

Sociedad Argentina de Inmunología.

The approved adjuvants for human use induce weak cellular immune responses in subunit vaccines. Thus, the development of new adjuvant strategies is critical. Recently, we have showed that a nanostructure from 6-O-ascorbyl palmitate (Coa-ASC16), used as a platform to formulate CpG-ODN, improved notably its adjuvanticity; one of the possible mechanisms involved is the controlled release given by Coa-ASC16 formulation. In addition, Coa-ASC16 elicits local inflammatory response but how it is sensed is little understood. Here, we begin to understand the underlying mechanisms on the interaction between Coa-ASC16 and immune system after i.p injection. We previously found that the inflammatory response elicited by Coa-ASC16 (neutrophils and monocytes recruitment and IL-1β, IL-6, IL-12) was dependent on MyD88 adaptor protein. TLR2, TLR4 and TLR7 were dispensable for this inflammatory effect. The administration of Coa-ASC16 was associated with the local release of double-stranded DNA (Coa- ASC16 vs control 2.5±0.5 vs 0.5±0.1 (μg/mL) (p<0.05)). In mice injected locally with DNase or in Tlr9-/- mice, the IL-6 production was inhibited compared to control (pg/mL: 442±167 vs 2231±378 (p<0,001) and 272.4±0.6 vs 1415±322 (p<0.01), respectively). Coa-ASC16 inflammatory activity is independent of NLRP3 signaling. In addition, Coa-ASC16 has itself adjuvant activity when is administrated with OVA antigen, which in turn requires MyD88 and IL-6 cytokine (Myd88-/- vs wt mice: IgG2c: 0.2±0.2 vs 1.6±0.2 (p<0,001), IFN-γ (pg/ml): not detected vs. 931±223; Il6-/- vs wt mice: IgG2c: 0.1±0.1 vs 2.8±0.5 (p<0.01), IFN-γ (pg/ml): 37±37 vs 254±104 (p<0.05)). Mice immunized with OVA were not reactive. Our results show a connection, given by IL-6 cytokine, between the innate and the adaptive response. Coa-ASC16 has not only a platform capacity but also an adjuvant function. Understanding the mechanisms of action of this biomaterial is important for development of safe and effective vaccines.