A synthetic analogue of phosphatidylinositol mannoside is an efficient adjuvant

Abstract

We recently described the synthesis of an ether linked analogue of phosphatidylinositol dimannoside (PIM₂ME). In the current study, PIM₂ME was found to significantly enhance the release of the key Th1 cytokine interleukin-12 (IL-12) by dendritic cells (DCs) of naïve mice in vitro, but not interleukin-10 (IL-10). Based on this result, it was hypothesized that PIM₂ME would be an effective adjuvant for cell-mediated immune responses. Injections of PIM₂ME alone did not lead to weight loss and did not have toxic side effects, based on biomarkers of toxicity in serum,demonstrating that the compound induced no apparent adverse side effects. Mice were vaccinated with the core antigens of the hepatitis C virus by itself or with three different adjuvants, namely PIM₂ME, a commercial preparation of monophosphoryl lipid A (MPL) or a preparation of aluminium hydroxide gel (alum). A control group of animals received the antigen only with no adjuvants. Immune responses to the Hepatitis C viral antigens were monitored by measuring antigen-specific production of interferon-gamma (IFN-γ), the p40 subunit of interleukin-12 (IL-12) and interleukin-10 (IL-10) to assess cell-mediated immune responses. Vaccination of mice with Hepatitis C viral antigens with the adjuvant PIM₂ME led to a significant increase in cell-mediated immune responses (IFN-γ and IL-12). Injection of Hepatitis C viral antigens in alum led to no enhancement of the cell-mediated immune response. We conclude that PIM₂ME is an efficacious adjuvant for enhancing cell-mediated immunity, and induces no observable adverse effects.

Keywords::

• Phosphatidylinositol mannoside
• adjuvant
• hepatitis C
• interferon
• interleukin-12

Acknowledgments

We thank Tania Wilson and Natalie Parlane for technical assistance. We thank Fiona Burke and Nereda Corbett (AgResearch) for care of the mice during this study and Louise Shaw (Gribbles) for coordinating and performing the biochemical analysis of the sera. This study was funded by the New Zealand Foundation for Research and Technology (contracts C08X0808 and PSAF IRLX0705).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the report.