A LIQUID CRYSTAL NANOSTRUCTURE, USED AS VACCINE PLATFORM, MODIFIES BIODISTRIBUTION OF VACCINE COMPONENTS

MARIN, CONSTANZA;SÁNCHEZ VALLECILLO, MARÍA F.;CHIODETTI, ANA L.;PALMA, SANTIAGO D.;MORÓN, GABRIEL;ALLEMANDI, DANIEL A.; PISTORESI-PALENCIA, MARÍA C.; MALETTO, BELKYS A

Congreso; Reunión Conjunta Sociedades de Biociencias; 2017

In the last years much effort in vaccinology has focused on the new formulation strategies for subunit vaccines. We formulated OVA (antigen) and CpG-ODN (TLR-9 agonist) with a nanostructure formed by self-assembly of 6-O-ascorbyl palmitate (Coa-ASC16). We have previously shown that this nanovaccine (OVA/CpG-ODN/Coa-ASC16) elicited an adaptive immune response superior to those induced by an aqueous formulation (OVA/CpG-ODN). However, we still do not know exactly the mechanisms of action of Coa-ASC16. Hence, the aim of this work was to test the impact of this nanoformulation on biodistribution of vaccine components and early immune response. Methods: mice were s.c. immunized with OVA/CpG-ODN or OVA/CpG-ODN/Coa-ASC16. OVA and CpG-ODN were labeled with near-infrared fluorescent dye, and both signals were measured with an Odyssey® CLx at several time points post immunization (pi). Cytokines/chemokines were evaluated in plasma by a multiplex assay at 1.5h pi. Results are indicated as OVA/CpG-ODN vs OVA/CpG-ODN/Coa-ASC16. Liver: OVA signal was 1.2 x 107 vs 0.6 x 107 (p<0.01), 4.3 x 107 vs 1.0 x 107 (p<0.001) and 2.0 x 107 vs 0.8 x 107 (p<0.01) at 20 min, 2 and 4h pi. No signal was observed in spleen and kidney in any of groups. Injection site: OVA signal was 1.6 x 106 vs 6.9 x 106 (p<0.001) and 0.05 x 106 vs 2.45 x 106 (p<0.05) at 0.3 and 5 days pi; for CpG-ODN there was no significant differences between both groups at any time. Lymph node: OVA signal was 1.8 x 105 vs 0.3 x 105 (p<0.01), 0.5 x 105 vs 4.5 x 105 (p<0.001) and 0.1 x 105 vs 2.8 x 105 (p<0.01) at 20 min, 2 and 24h pi; in contrast CpG-ODN signal was similar between two groups at 20 min and 2h pi. In addition, soluble vaccine elicited higher amounts of systemic TNF-α and MCP-1 than nanovaccine immunization (p<0.05). Conclusions: Coa-ASC16 retains antigen at the injection site but not CpG-ODN, and promotes co-delivery of both molecules to lymph node without concomitant induction of systemic inflammation.