Adjuvant activity of CpG-ODN formulated as a liquid crystal

• Published in: Biomaterials 2014-03, Vol.35 (8), p.2529-2542
• Main Authors: Sánchez Vallecillo, María F, Ullio Gamboa, Gabriela V, Palma, Santiago D, Harman, María F, Chiodetti, Ana L, Morón, Gabriel, Allemandi, Daniel A, Pistoresi-Palencia, María C, Maletto, Belkys A
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - pharmacokinetics; Advanced Basic Science; Alanine Transaminase - blood; Animals; Antigens - immunology; Ascorbic Acid - analogs & derivatives; Ascorbic Acid - chemistry; Ascorbic Acid - pharmacokinetics; Aspartate Aminotransferases - blood; Biological Availability; Cells, Cultured; Dentistry; Female; Immunity, Cellular; Immunization; Immunoglobulin G - immunology; Liquid Crystals - chemistry; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nanostructures - chemistry; Oligodeoxyribonucleotides - chemistry; Oligodeoxyribonucleotides - pharmacokinetics; Ovalbumin - immunology; Signal Transduction; Spleen - cytology; Spleen - metabolism; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Vaccines - chemistry; Vaccines - immunology
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.12.002

Abstract 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 I–III 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 Ly6Chigh 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.