Abstract
Despite the important role of adjuvants for vaccine development, relatively few adjuvants have been successfully incorporated into vaccines intended for human administration. This is in part due to the high toxicity associated with many experimental adjuvants. This lack of choice effectively hinders the ability to produce vaccines against many diseases, or to improve current vaccine formulations. The conjugation of immunostimulatory lipids to peptide antigens, to produce self-adjuvanting lipopeptide vaccines, has been tested in human clinical trials. These systems appear to have a number of advantages over more traditional adjuvants (e.g. alum salts) including the capacity for these vaccines to be administered via mucosal routes (e.g. orally or nasally) instead of by injection, elicitation of antigenspecific cytotoxic T-lymphocytes and mucosal immunity, as well as little-to-no observed toxicity. Several lipopeptide vaccine systems have been described in the literature, ranging from the conjugation of single fatty acid chains, to the conjugation of more complex lipids and glycolipids onto peptide antigens. The following review provides an overview of the most studied lipopeptide vaccine systems grouped into the following categories: 1) bacterial lipopeptides, including tri-palmitoyl-S-glyceryl cysteine (Pam3Cys) and di-palmitoyl- S-glyceryl cysteine (Pam2Cys); 2) the lipid-core peptide (LCP) and multiple antigen lipophilic adjuvant carrier (MALAC) systems; 3) single-chain palmitoylated peptides; and 4) glycolipids (e.g. monophosphoryl lipid A). The review also discusses the potential mechanisms of action for lipopeptide and glycolipopeptide vaccines, as well as structure activity relationships, and provides examples of studies utilising each system.
Keywords: Lipid core peptide system, lipids, lipopeptide vaccines, monophosphoryl lipid A, palmitic acid, Pam2Cys, Pam3Cys, peptide vaccines
Current Medicinal Chemistry
Title: Self-Adjuvanting Lipopeptide Vaccines
Volume: 15 Issue: 5
Author(s): Peter M. Moyle and Istvan Toth
Affiliation:
Keywords: Lipid core peptide system, lipids, lipopeptide vaccines, monophosphoryl lipid A, palmitic acid, Pam2Cys, Pam3Cys, peptide vaccines
Abstract: Despite the important role of adjuvants for vaccine development, relatively few adjuvants have been successfully incorporated into vaccines intended for human administration. This is in part due to the high toxicity associated with many experimental adjuvants. This lack of choice effectively hinders the ability to produce vaccines against many diseases, or to improve current vaccine formulations. The conjugation of immunostimulatory lipids to peptide antigens, to produce self-adjuvanting lipopeptide vaccines, has been tested in human clinical trials. These systems appear to have a number of advantages over more traditional adjuvants (e.g. alum salts) including the capacity for these vaccines to be administered via mucosal routes (e.g. orally or nasally) instead of by injection, elicitation of antigenspecific cytotoxic T-lymphocytes and mucosal immunity, as well as little-to-no observed toxicity. Several lipopeptide vaccine systems have been described in the literature, ranging from the conjugation of single fatty acid chains, to the conjugation of more complex lipids and glycolipids onto peptide antigens. The following review provides an overview of the most studied lipopeptide vaccine systems grouped into the following categories: 1) bacterial lipopeptides, including tri-palmitoyl-S-glyceryl cysteine (Pam3Cys) and di-palmitoyl- S-glyceryl cysteine (Pam2Cys); 2) the lipid-core peptide (LCP) and multiple antigen lipophilic adjuvant carrier (MALAC) systems; 3) single-chain palmitoylated peptides; and 4) glycolipids (e.g. monophosphoryl lipid A). The review also discusses the potential mechanisms of action for lipopeptide and glycolipopeptide vaccines, as well as structure activity relationships, and provides examples of studies utilising each system.
Export Options
About this article
Cite this article as:
Moyle M. Peter and Toth Istvan, Self-Adjuvanting Lipopeptide Vaccines, Current Medicinal Chemistry 2008; 15 (5) . https://dx.doi.org/10.2174/092986708783503249
DOI https://dx.doi.org/10.2174/092986708783503249 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Apoptosis in Drug Response
Current Pharmacogenomics FOXO Transcription Factors and their Role in Disorders of the Female Reproductive Tract
Current Drug Targets Intracellular Routing of Cytotoxic Pancreatic-Type Ribonucleases
Current Pharmaceutical Biotechnology Beyond Single Pathway Inhibition: MEK Inhibitors as a Platform for the Development of Pharmacological Combinations with Synergistic Anti-Leukemic Effects
Current Pharmaceutical Design Antineoplastic Activities, Apoptotic Mechanism of Action and Structural Properties of a Novel Silver(I) Chelate
Current Medicinal Chemistry The Influence of Lipophilicity on the Classification of Antitumor Acridinones Evaluated by Principal Component Analysis
Current Pharmaceutical Analysis 5-Nitro-Thiophene-Thiosemicarbazone Derivatives Present Antitumor Activity Mediated by Apoptosis and DNA Intercalation
Current Topics in Medicinal Chemistry Mitochondria and Familial Predisposition to Breast Cancer
Current Genomics A Novel Fusicoccin Derivative Preferentially Targets Hypoxic Tumor Cells and Inhibits Tumor Growth in Xenografts
Anti-Cancer Agents in Medicinal Chemistry Versatile and Valuable Utilization of Amidohydrolase L-glutaminase in Pharma and Food industries: A Review
Current Drug Metabolism Treatment Strategies for Multiple Myeloma in the Age of Novel Therapies
Current Cancer Therapy Reviews MicroRNA Dysregulation in the Myelodysplastic Syndromes
MicroRNA Folate-conjugated Chitosan-poly(ethylenimine) Copolymer As An Efficient and Safe Vector For Gene Delivery in Cancer Cells
Current Gene Therapy Microglia Phenotype Diversity
CNS & Neurological Disorders - Drug Targets Melatonin Induces Apoptosis and Inhibits the Proliferation of Cancer Cells via Reactive Oxygen Species-mediated MAPK and mTOR Pathways
Clinical Cancer Drugs Folate Based Radiopharmaceuticals for Imaging and Therapy of Cancer and Inflammation
Current Pharmaceutical Design Targeting Notch Pathway in Cancer Diagnostics and Therapeutics: An Emerging Approach
Recent Patents on Anti-Cancer Drug Discovery Immunological Aspects of Adult T-Cell Leukemia/Lymphoma (ATLL), a Possible Neoplasm of Regulatory T-Cells
Current Immunology Reviews (Discontinued) Novel Concepts in the Development of Platinum Antitumour Drugs: An Update
Medicinal Chemistry Reviews - Online (Discontinued) Targeting the Ubiquitin-Mediated Proteasome Degradation of p53 for Cancer Therapy
Current Pharmaceutical Design