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, Else M. Agger

Research output: Contribution to journalArticle

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-? production, increases considerably when TDB is present. High levels of IFN-? were observed for cationic liposomes; however, there was a marked reduction in IFN-? release over time. Conversely, for neutral liposomes containing TDB, although the initial amount of IFN-? 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.
LanguageEnglish
Pages1856-1865
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume100
Issue number5
Early online date10 Dec 2010
DOIs
Publication statusPublished - May 2011

Fingerprint

Subunit Vaccines
Liposomes
Trehalose
Antigens
Cholesterol
1,2-distearoyllecithin
dimethyldioctadecylammonium
Immunologic Factors
Immunity
Vaccines
Lipids

Keywords

  • immunologic adjuvants
  • animals
  • female
  • glycolipids
  • humans
  • interferon-gamma
  • liposomes
  • mice
  • inbred C57BL mice
  • phosphatidylcholines
  • quaternary ammonium compounds
  • recombinant fusion proteins
  • tuberculosis
  • tuberculosis vaccines
  • subunit vaccines

Cite this

McNeil, Sarah E. ; Rosenkrands, Ida ; Agger, Else Marie ; Andersen, Peter ; Perrie, Yvonne ; Agger, Else M. / Subunit vaccines distearoylphosphatidylcholine-based liposomes entrapping antigen offer a neutral alternative to dimethyldioctadecylammonium-based cationic liposomes as an adjuvant delivery system. In: Journal of Pharmaceutical Sciences. 2011 ; Vol. 100, No. 5. pp. 1856-1865.
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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-? production, increases considerably when TDB is present. High levels of IFN-? were observed for cationic liposomes; however, there was a marked reduction in IFN-? release over time. Conversely, for neutral liposomes containing TDB, although the initial amount of IFN-? 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.",
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Subunit vaccines distearoylphosphatidylcholine-based liposomes entrapping antigen offer a neutral alternative to dimethyldioctadecylammonium-based cationic liposomes as an adjuvant delivery system. / McNeil, Sarah E.; Rosenkrands, Ida; Agger, Else Marie; Andersen, Peter; Perrie, Yvonne; Agger, Else M.

In: Journal of Pharmaceutical Sciences, Vol. 100, No. 5, 05.2011, p. 1856-1865.

Research output: Contribution to journalArticle

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T1 - Subunit vaccines distearoylphosphatidylcholine-based liposomes entrapping antigen offer a neutral alternative to dimethyldioctadecylammonium-based cationic liposomes as an adjuvant delivery system

AU - McNeil, Sarah E.

AU - Rosenkrands, Ida

AU - Agger, Else Marie

AU - Andersen, Peter

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KW - female

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KW - humans

KW - interferon-gamma

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KW - inbred C57BL mice

KW - phosphatidylcholines

KW - quaternary ammonium compounds

KW - recombinant fusion proteins

KW - tuberculosis

KW - tuberculosis vaccines

KW - subunit vaccines

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