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

CONSTANZA MARIN; MARÍA F, SÁNCHEZ VALLECILLO; ANA LAURA CHIODETTI; BELKYS ANGELIZA MALETTO

Sao Paulo

Congreso; IUIS-Brazil Advanced Course of Vaccines; 2017

Instituto de Investigação em Imunologia/INCT, IUIS - International Union of Immunogical Societies, ALAI - Latin American Association on Immunological societies, Bill and Melinda Gates Foundation, Universidade de São Paulo and SBI- Brazilian Society of Imm

Actually, vaccinology is focused on new formulation strategies. 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 showed that OVA/CpG-ODN/Coa-ASC16 (G2), elicited an adaptive immune response superior to those induced by an aqueous formulation, OVA/CpG-ODN (G1). 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 G1 or G2. OVA and CpG-ODN were labeled with near-infrared fluorescent dye, and were measured with 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 G1 vs G2. 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 group. 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 were no differences between 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, G1 elicited higher amounts of systemic TNF-α and MCP-1 than G2 (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.