A LIQUID CRYSTAL OF ASCORBYL PALMITATE, USED AS VACCINE PLATFORM, PROVIDES CONTROLLED RELEASE OF ANTIGEN

MARÍA V. AGUIRRE, MARÍA F. SÁNCHEZ VALLECILLO, ANA L. CHIODETTI, MARÍA M. MINGUITO DE LA ESCALERA, CARLOS ARDAVÍN, SANTIAGO D. PALMA, GABRIEL MORÓN, DANIEL A. ALLEMANDI, MARÍA C. PISTORESI-PALENCIA, BELKYS A. MALETTO

Buenos Aires

Congreso; LXIII Reunión anual de SAI; 2015

Modern subunit vaccines require the development of new adjuvant strategies. CpG-ODN formulated with a liquid crystal nanostructure, formed by self-assembly of 6-O-ascorbyl palmitate (Coa-ASC16), is an attractive adjuvant system. We previously showed that Coa-ASC16 improves CpG-ODN's adjuvant activity; however, we still do not exactly understand how Coa-ASC16 operates. Coa-ASC16 alone is sensed by the innate immunity, triggering an inflammatory response at the injection site depending on MyD88 protein. The purpose of the present study was to uncover the mechanisms underlying the enhanced immune response by the formulation with Coa-ASC16. We determined antigen persistence at the injection site by in vivo near-infrared fluorescent imaging. Mice were subcutaneously injected with soluble dye-OVA or dye-OVA formulated with Coa-ASC16. The fluorescent signal of dye-OVA remaining at the injection site (expressed as % of maximum recorded value) was 4.8±0.8 vs 100±0 (p<0.001) and 0.1±0.1 vs 26.1±15.5 (p<0.05) 8h and 5 days after injection, respectively (dye-OVA vs dye-OVA formulated with Coa-ASC16). This could explain the results we obtained during an in vivo OT-II CD4+ T cell proliferation assay using CFSE dilution. Mice subcutaneously immunized with OVA/CpG-ODN/Coa-ASC16 showed higher absolute number of Vα2+ CD4+ T cells under proliferation in draining lymph node compared with mice immunized with OVA/CpG-ODN (7.1x105±1.1x105 vs 2.2x105±0.4x105, p<0.01). In conclusion, Coa-ASC16 works inducing a depot effect to maintain the antigen at the injection site, prolonging its interaction with the immune system. Coa-ASC16 used as a vaccine platform is effective due to the combination of the antigen controlled release and its intrinsic pro-inflammatory activity.