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Adjuvant activity of CpG-ODN formulated as a liquid crystal

机译：CpG-ODN制备为液晶的佐剂活性

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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 invitro 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.
机译：用重组/纯化的抗原批准的人疫苗批准的佐剂诱导细胞免疫反应弱，因此新的佐剂策略的发展至关重要。 CPG-ODN已成功被用作佐剂（I-III期临床试验），但需要改善其生物利用度。我们调查了用6-O-抗坏血基棕榈酸酯（COA-ASC16）的液晶纳米结构配制的CPG-ODN的佐剂能力。用OVA / CPG-ODN / COA-ASC16免疫的小鼠引发了有效的特异性IgG1，IgG2a，Th1和Th17细胞反应，而不会产生全身的不利影响。这些反应优于由OVA / CPG-ODN（OVA溶液与CPG-ODN的溶液）和由制剂ova / CpG-ODN / Al（OH）3诱导的那些响应优于那些。用OVA / CPG-ODN / COA-ASC16免疫导致长期的细胞介导的免疫反应（至少6.5个月）。此外，单独的CoA-ASC16允许受到CpG-ODN invitro的控制释放，并诱导局部炎症反应，与TLR4信号传导无关，其特征在于中性粒细胞和Ly6chigh单核细胞和促炎细胞因子的流入。值得注意的是，CPG-ODN共注入COA-ASC16（OVA / CPG-ODN PLUS COA-ASC16）的佐剂能力与OVA / CPG-ODN的佐剂活性类似，支持整个配方的要求以帮助CPG - odn authuviticity。这些结果表明了这种配方的潜力，开设了一种新的疫苗开发新的途径。

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  • 来源
    《Biomaterials》 |2014年第8期|共14页
  • 作者

    SánchezVallecilloM.F.; UllioGamboaG.V.; PalmaS.D.; HarmanM.F.; ChiodettiA.L.; MorónG.; AllemandiD.A.; Pistoresi-PalenciaM.C.; MalettoB.A.;

  • 作者单位

    Departamento de Bioquímica Clínica CIBICI (CONICET) Facultad de Ciencias Químicas Universidad;

    Departamento de Farmacia UNITEFA (CONICET) Facultad de Ciencias Químicas Universidad Nacional de;

    Departamento de Farmacia UNITEFA (CONICET) Facultad de Ciencias Químicas Universidad Nacional de;

    Departamento de Bioquímica Clínica CIBICI (CONICET) Facultad de Ciencias Químicas Universidad;

    Departamento de Bioquímica Clínica CIBICI (CONICET) Facultad de Ciencias Químicas Universidad;

    Departamento de Bioquímica Clínica CIBICI (CONICET) Facultad de Ciencias Químicas Universidad;

    Departamento de Farmacia UNITEFA (CONICET) Facultad de Ciencias Químicas Universidad Nacional de;

    Departamento de Bioquímica Clínica CIBICI (CONICET) Facultad de Ciencias Químicas Universidad;

    Departamento de Bioquímica Clínica CIBICI (CONICET) Facultad de Ciencias Químicas Universidad;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;
  • 关键词

    Adjuvant; Ascorbyl palmitate; CpG-ODN; Liquid crystal; Vaccine;

    机译：佐剂;抗坏血酸棕榈酸酯;CPG-ODN;液晶;疫苗;

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