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

MARÍN, C; SANCHEZ-VALLECILLO,MF; CHIODETTI, A; PALMA, S; MORÓN, G; ALLEMANDI, D; PISTORESI, MC; MALETTO, B

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencia; 2017

Sociedades de Biociencia

In the last years much effort in vaccinology has focused on the newformulation strategies for subunit vaccines. We formulated OVA (antigen)and CpG-ODN (TLR-9 agonist) with a nanostructure formedby self-assembly of 6-O-ascorbyl palmitate (Coa-ASC16). We havepreviously shown that this nanovaccine (OVA/CpG-ODN/Coa-ASC16) elicited an adaptive immune response superior to thoseinduced by an aqueous formulation (OVA/CpG-ODN). However, westill do not know exactly the mechanisms of action of Coa-ASC16.Hence, the aim of this work was to test the impact of this nanoformulationon biodistribution of vaccine components and early immuneresponse. Methods: mice were s.c. immunized with OVA/CpG-ODNor OVA/CpG-ODN/Coa-ASC16. OVA and CpG-ODN were labeledwith near-infrared fluorescent dye, and both signals were measuredwith an Odyssey® CLx at several time points post immunization (pi).Cytokines/chemokines were evaluated in plasma by a multiplex assayat 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 spleenand kidney in any of groups. Injection site: OVA signal was 1.6 x 106vs 6.9 x 106 (p<0.001) and 0.05 x 106 vs 2.45 x 106 (p<0.05) at 0.3and 5 days pi; for CpG-ODN there was no significant differencesbetween both groups at any time. Lymph node: OVA signal was 1.8x 105 vs 0.3 x 105 (p<0.01), 0.5 x 105 vs 4.5 x 105 (p<0.001) and 0.1x 105 vs 2.8 x 105 (p<0.01) at 20 min, 2 and 24h pi; in contrast CpGODNsignal was similar between two groups at 20 min and 2h pi. Inaddition, soluble vaccine elicited higher amounts of systemic TNF-αand 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 withoutconcomitant induction of systemic inflammation.