Immunogenicity of Liposomes Containing Lipid Core Peptides and the Adjuvant Quil A
| Autor: | Thomas Rades, Istvan Toth, Sarah Hook, Karen L. White, Philip Kearns |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Chemistry
Pharmaceutical Injections Subcutaneous Lipoproteins medicine.medical_treatment T cell Antigen presentation Antigens Differentiation Myelomonocytic Epitopes T-Lymphocyte Pharmaceutical Science Bone Marrow Cells Biology Cancer Vaccines Quillaja Saponins Mice Immune system Adjuvants Immunologic Antigen Antigens CD medicine Animals Cytotoxic T cell Pharmacology (medical) Cells Cultured Phospholipids Cell Proliferation Pharmacology Liposome Immunogenicity Organic Chemistry Dendritic Cells Neoplasms Experimental Saponins Molecular biology Peptide Fragments Mice Inbred C57BL medicine.anatomical_structure Liposomes Molecular Medicine Mannose Adjuvant T-Lymphocytes Cytotoxic Biotechnology |
| Zdroj: | Pharmaceutical Research. 23:1473-1481 |
| ISSN: | 1573-904X 0724-8741 |
| DOI: | 10.1007/s11095-006-0272-z |
| Popis: | Purpose. 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 naive 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. Conclusion. ManLCPs administered in liposomes are able to stimulate strong cytotoxic and protective immune responses if Quil A is also incorporated as an adjuvant. |
| Databáze: | OpenAIRE |
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