ANTIBODY AND CD8+ T-CELL RESPONSES IN IMMUNIZED MICE WITH DIFFERENT VACCINATION STRATEGIES

FEDERICO DANIEL RUIZ MORENO; CONSTANZA MARIN; FERNANDA SÁNCHEZ-VALLECILLO; ANA CHIODETTI; FLORENCIA RIVELLI; GABRIEL MORÓN; DANIEL ALLEMANDI; MARÍA C PISTORESI- PALENCIA; SANTIAGO PALMA; BELKYS A. MALETTO

Mar del Plata

Congreso; LXVI Reunión de la Sociedad Argentina de Inmunología; 2018

Subunit-vaccines require the development of new adjuvant strategies. Recently, CpG-ODN was approved by FDA for a human vaccine. However, the free CpG-ODN present some limitations that restrict its bioavailability. In this context, we nanoformulated CpG-ODN with a nanostructure (Coa-ASC16) formed by self-assembly of 6-O-ascorbyl palmitate. Here, we investigated the effect of various formulations on antigen-specific response. Mice were subcutaneously immunized with a single-dose of OVA and CpG-ODN in solution (OC), OVA and CpG-ODN nanoformulated with Coa-ASC16 (OCC), OVA and CpG-ODN in solution heated at 80ºC for 15 min and then cooled down to room temperature to simulate the conditions of preparation of the nanostructured formulation (OCø), and OVA formulated with Montanide Gel 01 PR (reference adjuvant) (OM). OVA-specific IgG and IgG2a titers were evaluated by ELISA in all groups and SIINFEKL-Kb tetramer+ CD8+ T-cells by flow cytometry in OCC and OCø groups. Antibody response: OCø developed IgG response faster than other groups (day 8: 2.40±0.17), OCC and OC seroconverted on day 10 (2.00±0.66 and 1.35±0.19), and OM on day 13 (1.43±0.54). OCC induced higher IgG titers than OC and OM (p<0.05) but comparable to that induced by OCø on day 13, 16, 20, 28 and 35. IgG2c was only induced by OCC and OCø, and titers were comparable between both groups (day 16: 1.7±0.26 and 2.03±0.26; day 20: 2.2±0.1 and 2.1±0.25). CD8+ T-cell response: OCC elicited a higher expansion of SIINFEKL-Kb tetramer+ CD8+ T-cells than mice immunized with OCø (3.95±0.93 vs 0.82±0.23, p<0.05). Conclusions: OCC and OCø induced better titers and quality of antibody response than OC but OCC is superior to OCø in inducing CD8+ T-cell response. These results showed how various antigen-adjuvant formulations impact the resultant adaptive immune response. Further investigations are required to understand the precise underlying mechanisms.