Journal
BIOMATERIALS
Volume 35, Issue 8, Pages 2529-2542Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.12.002
Keywords
CpG-ODN; Adjuvant; Vaccine; Ascorbyl palmitate; Liquid crystal
Funding
- Agencia Nacional de Promocion Cientifica y Tecnica (PICT-MICINN) [2772]
- Secretaria de Ciencia y Tecnica de la Universidad Nacional de Cordoba and the Ministerio de Ciencia y Tecnologia de la Provincia de Cordoba (PID)
- CONICET [11220090100109]
- PhD fellowship from the Agencia Nacional de Promocion Cientifica y Tecnica
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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 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. (C) 2013 Elsevier Ltd. All rights reserved.
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