MF59 Emulsion Is an Effective Delivery System for a Synthetic TLR4 Agonist (E6020)
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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.
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- MF59 Emulsion Is an Effective Delivery System for a Synthetic TLR4 Agonist (E6020)
Volume 26, Issue 6 , pp 1477-1485
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- influenza vaccine delivery
- toll like receptor agonists
- T-cell cytokine response
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- 1. Novartis Vaccines, Via Fiorentina 1, 53100, Siena, Italy
- 2. Novartis Vaccines, 45 Sidney Street, Cambridge, MA, 02139, USA
- 3. Eisai Research Institute, 4 Corporate Drive, Andover, MA, 01742, USA