Adjuvant activity of CpG-ODN formulated as a liquid crystal

SANCHEZ VALLECILLO, MARIA FERNANDA; ULLIO GAMBOA, GABRIELA; PALMA S. D; HARMAN MF; CHIODETTI A; MORON GABRIEL; ALLEMANDI D,; PISTORESI, M. C.; MALETTO, BELKYS

BIOMATERIALS

ELSEVIER SCI LTD

Lugar: Amsterdam; Año: 2014 vol. 35 p. 2529 - 2542

0142-9612

The adjuvants approved in human vaccine with recombinant/purified antigens induce weak cellular immune response and so the development of new adjuvant strategies is critical. CpG-ODN has successfully been used as an adjuvant (phase IeIII clinical trials) but its bioavailability needs to be improved. We investigated the adjuvant ability of CpG-ODN formulated with a liquid crystal nanostructure of 6-O ascorbyl palmitate (Coa-ASC16). Mice immunized with OVA/CpG-ODN/Coa-ASC16 elicited a potent specific IgG1, IgG2a, Th1 and Th17 cellular response without systemic adverse effects. These responses were superior to those induced by OVA/CpG-ODN (solution of OVA with CpG-ODN) and to those induced by the formulation OVA/CpG-ODN/Al(OH)3. Immunization with OVA/CpG-ODN/Coa-ASC16 resulted in a long-lasting cell-mediated immune response (at least 6.5 months). Furthermore, Coa-ASC16 alone allows a controlled release of CpG-ODN in vitro and induces local inflammatory response, independent of TLR4 signaling, characterized by an influx of neutrophils and Ly6C high monocytes and pro-inflammatory cytokines. Remarkably, the adjuvant capacity of CpG-ODN co injected with Coa-ASC16 (OVA/CpG-ODN plus Coa-ASC16) was similar to the adjuvant activity of OVA/CpG-ODN, supporting the requirement for whole formulation to help CpG-ODN adjuvanticity. These results show the potential of this formulation, opening a new avenue for the development of better vaccines.