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.


BACKGROUND
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.
Jain
Vikas
V
Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, India.
Vyas
Suresh P
SP
Kohli
Dharmveer V
DV
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000737:chemistry* / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D004075:Diglycerides / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000166:cytology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D013154:Spleen / Q000166:cytology
D000276:Adjuvants, Immunologic; D004075:Diglycerides; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D008081:Liposomes; C005071:dipalmitin; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma