MF59 Emulsion Is an Effective Delivery System for a Synthetic TLR4 Agonist (E6020)
MF59 Emulsion Is an Effective Delivery System for a Synthetic TLR4 Agonist (E6020)
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MF59 乳化液是合成 TLR4 激动剂 (E6020) 的有效输送系统
DOI：
10.1007/s11095-009-9859-5
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发表时间：
2009-06-01
影响因子：
3.7
通讯作者：
O'Hagan, Derek T.
中科院分区：
文献类型：
--
作者：
Baudner, Barbara C.;Ronconi, Vanessa;O'Hagan, Derek T.
疫苗的效力取决于接种者的年龄和免疫能力。传统的非佐剂流感疫苗在老年人中并不理想，需要预防流感能力增强的疫苗。TLR4激动剂E6020单独给药或与MF59联合给药，并与MF59和TLR9激动剂CpG进行比较。研究了其增强抗体滴度和调节对亚单位流感疫苗免疫反应质量的能力。小鼠分别用抗原单独、MF59或TLR激动剂单独或它们的组合免疫。检测血清中IgG抗体滴度和血凝抑制（HI）滴度。Th1/Th2型反应通过血清样品中IgG亚类的滴定和脾细胞中t细胞细胞因子的反应来确定。与所有替代佐剂相比，MF59是诱导HI和t细胞反应的最佳单一佐剂。E6020或CpG与MF59共同递送并没有进一步增加抗体滴度，而是转向了更基于Th1的免疫反应。结合像E6020和MF59这样的佐剂可以更精细地调整针对特定Th偏倚的免疫反应，因此对改进流感疫苗的开发具有重要意义。
The effectiveness of vaccines depends on the age and immunocompetence of the vaccinee. Conventional non-adjuvanted influenza vaccines are suboptimal in the elderly and vaccines with improved ability to prevent influenza are required. The TLR4 agonist E6020, either given alone or co-delivered with MF59, was evaluated and compared to MF59 and the TLR9 agonist CpG. Its ability to enhance antibody titres and to modulate the quality of the immune response to a subunit influenza vaccine was investigated.Mice were immunized with either antigens alone, with MF59 or with the TLR agonists alone, or with a combination thereof. Serum samples were assayed for IgG antibody titres and hemagglutination inhibition (HI) titres. Th1/Th2 type responses were determined by titrating IgG subclasses in serum samples and by T-cell cytokine responses in splenocytes.MF59 was the best single adjuvant inducing HI and T-cell responses in comparison to all alternatives. The co-delivery of E6020 or CpG with MF59 did not further increase antibody titres however shifted towards a more Th1 based immune response.Combining adjuvants like E6020 and MF59 allowed a finer tuning of the immune response towards a particular Th bias, thus have significant implications for the development of improved influenza vaccines.