Baudner Barbara C, Ronconi Vanessa, Casini Daniele, Tortoli Marco, Kazzaz Jina, Singh Manmohan, Hawkins Lynn D, Wack Andreas, O'Hagan Derek T
Novartis Vaccines, Via Fiorentina 1, Siena, Italy.
Pharm Res. 2009 Jun;26(6):1477-85. doi: 10.1007/s11095-009-9859-5. Epub 2009 Mar 3.
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.
疫苗的有效性取决于接种者的年龄和免疫能力。传统的无佐剂流感疫苗在老年人中效果欠佳，因此需要研发预防流感能力更强的疫苗。对单独使用或与MF59共同递送的Toll样受体4（TLR4）激动剂E6020进行了评估，并与MF59和Toll样受体9（TLR9）激动剂CpG进行比较。研究了其增强抗体滴度以及调节对亚单位流感疫苗免疫反应质量的能力。
用单独的抗原、MF59、单独的TLR激动剂或它们的组合对小鼠进行免疫。检测血清样本中的IgG抗体滴度和血凝抑制（HI）滴度。通过滴定血清样本中的IgG亚类和脾细胞中的T细胞细胞因子反应来确定Th1/Th2型反应。
与所有其他佐剂相比，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提高抗体滴度，但使免疫反应向更偏向Th1的方向转变。
将E6020和MF59等佐剂联合使用，可以更精细地调节免疫反应，使其偏向特定的Th偏差，因此对改进流感疫苗的研发具有重要意义。
