Effective induction of CD8+ T-cell response using CpG oligodeoxynucleotides and HER-2/neu-derived peptide co-encapsulated in liposomes.
CpG oligodeoxynucleotides (CpG ODN) have been shown to have potent adjuvant activity for a wide range of antigens. Of particular interest is their improved activity when closely associated with the antigen. The purpose of this study is to determine the potential benefit of liposomes as a co-delivery vehicle to enhance the adjuvant activity of CpG ODN for a HER-2/neu-derived peptide to induce CD8+ T-cell response. Immunization studies were performed to evaluate the effectiveness of the liposomal vaccine in BALB/c mice. Mice were immunized with p63-71 encapsulated in liposomes alone or in combination with CpG ODN, as well as p63-71 alone in saline or with peptide-pulsed dendritic cells (DC) as controls. Enzyme-linked immunospot assay (ELISPOT) assay was performed to measure the frequency of splenocytes secreting IFN-gamma as a means to determine the antigen-specific response. It was found that immunization using p63-71 co-encapsulated with CpG ODN within the same liposomes enhanced the antigen-specific IFN-gamma response by more than 100-fold when compared with mice immunized with p63-71 alone. Immunization using free CpG ODN plus p63-71 encapsulated in liposomes or p63-71 and CpG ODN encapsulated in separate liposomes could not achieve the same effect. Using CD8 as a second marker and intracellular flow cytometric analysis, it was found that the IFN-gamma response was contributed by CD8+ T-cells, confirming the induction of cytotoxic T-lymphocytes (CTL) by this vaccination method. This indicates that a close association of HER-2/neu peptide and CpG ODN inside liposomes enhances the CTL epitope delivery and induces CD8+ mediated immune response. These results suggest that a vaccinal approach using liposome delivery system carrying in self-tumoral epitope and CpG ODN as adjuvant may have important implications for cancer therapy.
Li
Wai Ming
WM
Department of Pathology and Laboratory Medicine, Faculty of Medicine, The University of British Columbia, BC, Vancouver, Canada.
Dragowska
Wieslawa H
WH
Bally
Marcel B
MB
Schutze-Redelmeier
Marie Paule
MP
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology*; D003713:Dendritic Cells / Q000378:metabolism; D004339:Drug Compounding; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005620:Freund's Adjuvant; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism
D005620:Freund's Adjuvant; D007371:Interferon-gamma; D008081:Liposomes; D009841:Oligonucleotides; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases