MF59 Emulsion Is an Effective Delivery System for a Synthetic TLR4 Agonist (E6020)

被引:69
作者
Baudner, Barbara C. [1 ]
Ronconi, Vanessa [1 ]
Casini, Daniele [1 ]
Tortoli, Marco [1 ]
Kazzaz, Jina [2 ]
Singh, Manmohan [2 ]
Hawkins, Lynn D. [3 ]
Wack, Andreas [1 ]
O'Hagan, Derek T. [1 ]
机构
[1] Novartis Vaccines, I-53100 Siena, Italy
[2] Novartis Vaccines, Cambridge, MA 02139 USA
[3] Eisai Res Inst, Andover, MA 01742 USA
关键词
adjuvants; influenza vaccine delivery; MF59; toll like receptor agonists; T-cell cytokine response; HEPATITIS-B-VACCINE; T-CELL RESPONSES; MF59-ADJUVANTED INFLUENZA VACCINE; RECOMBINANT GLYCOPROTEIN VACCINE; ANTIBODY-RESPONSES; RECEPTOR AGONISTS; IMMUNE-RESPONSE; ADJUVANT MF59; IMMUNOGENICITY; SAFETY;
D O I
10.1007/s11095-009-9859-5
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:1477 / 1485
页数:9
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