Self-adjuvanting lipopeptide vaccines.

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  • Author(s): Moyle PM;Moyle PM; Toth I
  • Source:
    Current medicinal chemistry [Curr Med Chem] 2008; Vol. 15 (5), pp. 506-16.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 9440157 Publication Model: Print Cited Medium: Print ISSN: 0929-8673 (Print) Linking ISSN: 09298673 NLM ISO Abbreviation: Curr Med Chem Subsets: MEDLINE
    • Publication Information:
      Publication: Saif Zone, Sharjah, U.A.E. : Bentham Science Publishers
      Original Publication: Schiphol, The Netherlands : Bentham Science Publishers,
    • Subject Terms:
      Adjuvants, Immunologic*; Lipids/*immunology ; Peptide Fragments/*immunology ; Vaccines, Synthetic/*immunology; Cysteine/analogs & derivatives ; Cysteine/immunology ; Humans ; Lipid A/analogs & derivatives ; Lipid A/immunology ; Lipoproteins/immunology ; Lipoylation ; Structure-Activity Relationship
    • 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 antigen-specific 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.
    • Number of References:
      136
    • Accession Number:
      0 (Adjuvants, Immunologic)
      0 (Lipid A)
      0 (Lipids)
      0 (Lipoproteins)
      0 (Peptide Fragments)
      0 (Vaccines, Synthetic)
      87420-41-5 (2,3-bis(palmitoyloxy)-2-propyl-1-palmitoylcysteine)
      K848JZ4886 (Cysteine)
      MWC0ET1L2P (monophosphoryl lipid A)
    • Publication Date:
      Date Created: 20080222 Date Completed: 20080501 Latest Revision: 20190823
    • Publication Date:
      20221213
    • Accession Number:
      10.2174/092986708783503249
    • Accession Number:
      18289006