Immunogenicity of liposomes containing lipid core peptides and the adjuvant Quil A.
OBJECTIVE
The purpose of this study was to investigate the immunogenicity of liposomes containing mannosylated lipid core peptide (manLCP) constructs, both in vitro and in vivo, with or without the addition of the immune stimulating adjuvant Quil A.


METHODS
Mouse bone marrow dendritic cells (BMDC) were cultured with liposome formulations for 48 h, and the resulting level of BMDC activation was determined by flow cytometry. BMDC pulsed with liposome formulations were incubated with 5,6-carboxyfluoroscein diacetate succinimidyl ester-labeled T cells for 72 h and the resulting T cell proliferation was determined by flow cytometry. To investigate the immunogenicity of formulations in vivo, groups of C57Bl/6J mice were immunized by subcutaneous injection, and the resulting antigen-specific cytotoxic and protective immune responses toward tumor challenge evaluated.


RESULTS
Despite being unable to demonstrate the activation of BMDC, BMDC pulsed with liposomes containing manLCP constructs were able to stimulate the proliferation of naïve T cells in vitro. However, in vivo only liposomes containing both manLCP and Quil A were able to stimulate a strong antigen-specific cytotoxic immune response. Liposomes containing manLCP and Quil A within the same particle were able to protect against the growth of tumor cells to a similar level as if the antigen was administered in alum with CD4 help.


CONCLUSIONS
ManLCPs administered in liposomes are able to stimulate strong cytotoxic and protective immune responses if Quil A is also incorporated as an adjuvant.
White
Karen
K
School of Pharmacy, University of Otago, PO Box 913, Dunedin, New Zealand.
Rades
Thomas
T
Kearns
Philip
P
Toth
Istvan
I
Hook
Sarah
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D007279:Injections, Subcutaneous; D008074:Lipoproteins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D008081:Liposomes / Q000737:chemistry; D008358:Mannose / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D010743:Phospholipids / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D062605:Quillaja Saponins; D012503:Saponins / Q000008:administration & dosage / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000097382:CD68 Molecule
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D008074:Lipoproteins; D008081:Liposomes; D008358:Mannose; D010446:Peptide Fragments; D010743:Phospholipids; D062605:Quillaja Saponins; D012503:Saponins; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C046386:Quil A