Subunit vaccines: distearoylphosphatidylcholine-based liposomes entrapping antigen offer a neutral alternative to dimethyldioctadecylammonium-based cationic liposomes as an adjuvant delivery system

Sarah E. McNeil, Ida Rosenkrands, Else Marie Agger, Peter Andersen, Yvonne Perrie

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The adjuvanticity of liposomes can be directed through formulation to develop a safe yet potent vaccine candidate. With the addition of the cationic lipid dimethyldioctadecylammonium bromide (DDA) to stable neutral distearoylphosphatidylcholine (DSPC):cholesterol (Chol) liposomes, vesicle size reduces while protein entrapment increases. The addition of the immunomodulator, trehalose 6,6-dibehenate (TDB) to either the neutral or cationic liposomes did not affect the physiochemical characteristics of these liposome vesicles. However, the protective immune response, as indicated by the amount of IFN-γ production, increases considerably when TDB is present. High levels of IFN-γ were observed for cationic liposomes; however, there was a marked reduction in IFN-γ release over time. Conversely, for neutral liposomes containing TDB, although the initial amount of IFN-γ was slightly lower than the cationic equivalent, the overall protective immune responses of these neutral liposomes were effectively maintained over time, generating good levels of protection. To that end, although the addition of DSPC and Chol reduced the protective immunity of DDA:TDB liposomes, relatively high protection was observed for the neutral counterpart, DSPC:Chol:TDB, which may offer an effective neutral alternative to the DDA:TDB cationic system, especially for the delivery of either zwitterionic (neutral) or cationic molecules or antigens.

Original languageEnglish
Pages (from-to)1856-1865
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume100
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • vaccine adjuvant
  • protein delivery
  • subunit vaccines
  • immunology

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