Use of a liposome antigen delivery system to alter immune responses in vivo

J Pharm Sci. 1998 Nov;87(11):1428-32. doi: 10.1021/js980075p.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Amino Acid Sequence
  • Animals
  • Drug Carriers
  • Drug Delivery Systems*
  • Female
  • Hepatitis B Core Antigens / administration & dosage*
  • Hepatitis B Core Antigens / chemistry
  • Hepatitis B Core Antigens / immunology
  • Hepatitis B Vaccines / administration & dosage*
  • Hepatitis B Vaccines / immunology
  • Liposomes
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • T-Lymphocytes / immunology

Substances

  • Adjuvants, Immunologic
  • Drug Carriers
  • Hepatitis B Core Antigens
  • Hepatitis B Vaccines
  • Liposomes