MF59 emulsion is an effective delivery system for a synthetic TLR4 agonist (E6020)

Pharm Res. 2009 Jun;26(6):1477-85. doi: 10.1007/s11095-009-9859-5. Epub 2009 Mar 3.

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.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • Cytokines / immunology
  • Drug Delivery Systems / methods
  • Female
  • Hemagglutination Inhibition Tests
  • Immunization
  • Immunoglobulin G / immunology
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology
  • Mice
  • Mice, Inbred BALB C
  • Polysorbates / administration & dosage*
  • Squalene / administration & dosage*
  • Squalene / immunology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Toll-Like Receptor 4 / agonists*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Cytokines
  • Immunoglobulin G
  • Influenza Vaccines
  • MF59 oil emulsion
  • Polysorbates
  • Toll-Like Receptor 4
  • Squalene