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

Autor: Barbara Baudner, Vanessa Ronconi, Daniele Casini, Marco Tortoli, Jina Kazzaz, Manmohan Singh, Lynn Hawkins, Andreas Wack, Derek O’Hagan
Předmět:
Zdroj: Pharmaceutical Research; Jun2009, Vol. 26 Issue 6, p1477-1485, 9p
Abstrakt: Abstract Purpose  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. Methods  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. Results  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. Conclusion  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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index