TLR4 ligand formulation causes distinct effects on antigen-specific cell-mediated and humoral immune responses

Vaccine. 2013 Dec 2;31(49):5848-55. doi: 10.1016/j.vaccine.2013.09.069. Epub 2013 Oct 10.


The formulation of TLR ligands and other immunomodulators has a critical effect on their vaccine adjuvant activity. In this work, the synthetic TLR4 ligand GLA was formulated with three distinct vaccine delivery system platforms (aqueous suspension, liposome, or oil-in-water emulsion). The effect of the different formulations on the adaptive immune response to protein subunit vaccines was evaluated in the context of a recombinant malaria antigen, Plasmodium berghei circumsporozoite protein (PbCSP). Antibody responses in vaccinated mice were similar for the different formulations of GLA. However, cell-mediated responses differed significantly depending on the adjuvant system; in particular, the emulsion formulation of the TLR4 ligand induced significantly enhanced cellular IFN-γ and TNF-α responses compared to the other formulations. The effects of differences in adjuvant formulation composition and physical characteristics on biological activity are discussed. These results illustrate the importance of formulation of immunostimulatory adjuvants (e.g. TLR ligands) on the resulting immune responses to adjuvanted vaccines and may play a critical role for combating diseases where T cell immunity is advantageous.

Keywords: Aqueous nanosuspension; Glucopyranosyl lipid adjuvant; Liposome; Oil-in-water emulsion; Th1-type immunity; Vaccine adjuvant formulation.

Publication types

  • Comparative Study

MeSH terms

  • Adaptive Immunity
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antigens, Protozoan / immunology*
  • Female
  • Immunity, Cellular
  • Immunity, Humoral
  • Interferon-gamma / immunology
  • Ligands
  • Malaria Vaccines / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Plasmodium berghei / immunology
  • T-Lymphocytes / immunology
  • Toll-Like Receptor 4 / agonists*
  • Toll-Like Receptor 4 / immunology
  • Tumor Necrosis Factor-alpha / immunology
  • Vaccines, Subunit / immunology


  • Adjuvants, Immunologic
  • Antigens, Protozoan
  • Ligands
  • Malaria Vaccines
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Vaccines, Subunit
  • Interferon-gamma