MF59 Emulsion Is an Effective Delivery System for a Synthetic TLR4 Agonist (E6020)
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- Baudner, B.C., Ronconi, V., Casini, D. et al. Pharm Res (2009) 26: 1477. doi:10.1007/s11095-009-9859-5
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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.