Use of a liposome antigen delivery system to alter immune responses in vivo.
It has been reported that a certain peptide encompassing residues 129-140 of the hepatitis B virus core antigen (HBcAg) leads to a Th2-type response in C57BL/10 mice. We postulated that by formulating the peptide in liposomes along with an immune modulator known as MPLA the immune response could be directed toward a Th1-type response. If these liposomes could deliver the peptide along with MPLA to antigen presenting cells, then the immune response generated could be polarized to a Th1 response. The type of immune response initiated after immunization with the peptide HBcAg (126-140) in different formulations was determined by an ex vivo T cell proliferation assay and by analysis of the cytokine profile of the proliferating T cells. A group of C57BL/6 mice immunized with peptide plus MPLA in a liposome formulation displayed a strong T cell proliferative response. The T cell subset was identified as Th1 based on the cytokine profile. The cytokine profiles showed significant production of interferon-gamma (IFN-gamma, a Th1-type cytokine) and extremely low levels of interleukin-4 (IL-4, a Th2-type cytokine). The control group of C57BL/6 mice immunized with peptide plus alum showed a very low level of T cell proliferation, and no increase was seen in IFN-gamma or IL-4 production. These data signify that a Th1-type response occurred in mice treated with peptide in a liposome formulation but not in mice treated with the control formulation.
Lutsiak
C M
CM
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Sosnowski
D L
DL
Wishart
D S
DS
Kwon
G S
GS
Samuel
J
J
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D006512:Hepatitis B Core Antigens / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D008081:Liposomes