Well-defined and potent liposomal hepatitis B vaccines adjuvanted with lipophilic MDP derivatives

The characterization of immunological cascades of the innate immune system activated by invariant molecular structures termed as pathogen-associated molecular patterns recognized by pattern recognition receptors of macrophages and dendritic cells, have allowed the elucidation of the mechanisms underlying the immunomodulatory properties of adjuvants. Thus, adjuvant-active lipophilic analogues of N-acetyl muramyl dipeptide (MDP) were incorporated in liposomal hepatitis B surface antigen (HBsAg) formulations. The immunoreactivity of the formulations was evaluated by measuring anti-HBs, immunoglobulin G (IgG), and isotype antibody titer and compared with alum-adsorbed HBsAg formulation. The formulations were also evaluated for cell-mediated immune response by HBsAg-specific proliferation of splenocytes and simultaneous estimation of cytokines (interleukin-4 [IL-4], interferon-gamma [IFN-gamma]). Results indicate that the serum IgG and anti-HBs titer obtained after intramuscular administration of liposomal muramyl tripeptide-phosphatidylethanolamine (MTP-PE) and liposomal N-acetylmuramyl-l-alanyl-d-isoglutamine-glycerol dipalmitate (MDP-GDP) antigenic formulations were significantly higher. The incorporation of MTP-PE on the liposomal HBsAg increased the stimulation index (SI) four to five times as compared to plain HBsAg solution, and it also induced significantly higher Th1 cellular immune response with a predominant IFN-gamma level. So it is the novel effective and potentially safe approach in which liposomes act as delivery vehicles for hepatitis B viral antigen to antigen-presenting cells and is ornamented with a biological response modifier that could activate these target cells to enhance the antigen presentation to T lymphocytes.

In this study, adjuvant-active lipophilic analogues on N-acetyl muramyl dipeptide (MDP) were incorporated in liposomal hepatitis B surface antigen (HBsAg) formulations. The immunoreactivity of the formulations was evaluated and found effective, leading to a potentially enhanced immune response against the delivered antigen.