Pharmaceutical Research

, Volume 26, Issue 6, pp 1477–1485

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

  • Barbara C. Baudner
  • Vanessa Ronconi
  • Daniele Casini
  • Marco Tortoli
  • Jina Kazzaz
  • Manmohan Singh
  • Lynn D. Hawkins
  • Andreas Wack
  • Derek T. O’Hagan
Research Paper

DOI: 10.1007/s11095-009-9859-5

Cite this article as:
Baudner, B.C., Ronconi, V., Casini, D. et al. Pharm Res (2009) 26: 1477. doi:10.1007/s11095-009-9859-5

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.

KEY WORDS

adjuvantsinfluenza vaccine deliveryMF59toll like receptor agonistsT-cell cytokine response

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Barbara C. Baudner
    • 1
  • Vanessa Ronconi
    • 1
  • Daniele Casini
    • 1
  • Marco Tortoli
    • 1
  • Jina Kazzaz
    • 2
  • Manmohan Singh
    • 2
  • Lynn D. Hawkins
    • 3
  • Andreas Wack
    • 1
  • Derek T. O’Hagan
    • 1
  1. 1.Novartis VaccinesSienaItaly
  2. 2.Novartis VaccinesCambridgeUSA
  3. 3.Eisai Research InstituteAndoverUSA