Small cationic DDA:TDB liposomes as protein vaccine adjuvants obviate the need for TLR agonists in inducing cellular and humoral responses

Anita Milicic, Randip Kaur, Arturo Reyes-Sandoval, Choon-Kit Tang, Jared Honeycutt, Yvonne Perrie, Adrian V. S. Hill

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Most subunit vaccines require adjuvants in order to induce protective immune responses to the targeted pathogen. However, many of the potent immunogenic adjuvants display unacceptable local or systemic reactogenicity. Liposomes are spherical vesicles consisting of single (unilamellar) or multiple (multilamellar) phospholipid bi-layers. The lipid membranes are interleaved with an aqueous buffer, which can be utilised to deliver hydrophilic vaccine components, such as protein antigens or ligands for immune receptors. Liposomes, in particular cationic DDA:TDB vesicles, have been shown in animal models to induce strong humoral responses to the associated antigen without increased reactogenicity, and are currently being tested in Phase I human clinical trials. We explored several modifications of DDA:TDB liposomes--including size, antigen association and addition of TLR agonists--to assess their immunogenic capacity as vaccine adjuvants, using Ovalbumin (OVA) protein as a model protein vaccine. Following triple homologous immunisation, small unilamellar vesicles (SUVs) with no TLR agonists showed a significantly higher capacity for inducing spleen CD8 IFNγ responses against OVA in comparison with the larger multilamellar vesicles (MLVs). Antigen-specific antibody reponses were also higher with SUVs. Addition of the TLR3 and TLR9 agonists significantly increased the adjuvanting capacity of MLVs and OVA-encapsulating dehydration-rehydration vesicles (DRVs), but not of SUVs. Our findings lend further support to the use of liposomes as protein vaccine adjuvants. Importantly, the ability of DDA:TDB SUVs to induce potent CD8 T cell responses without the need for adding immunostimulators would avoid the potential safety risks associated with the clinical use of TLR agonists in vaccines adjuvanted with liposomes.

LanguageEnglish
Article numbere34255
Number of pages10
JournalPLOS One
Volume7
Issue number3
DOIs
Publication statusPublished - 2012

Fingerprint

vaccine adjuvants
Unilamellar Liposomes
humoral immunity
Liposomes
agonists
ovalbumin
Vaccines
antigens
Ovalbumin
Antigens
vaccines
Proteins
proteins
subunit vaccines
Immunization
rehydration
Clinical Trials, Phase I
Subunit Vaccines
T-cells
Fluid Therapy

Keywords

  • liposomes
  • DDA:TDB
  • adjuvants
  • humoral responses

Cite this

Milicic, Anita ; Kaur, Randip ; Reyes-Sandoval, Arturo ; Tang, Choon-Kit ; Honeycutt, Jared ; Perrie, Yvonne ; Hill, Adrian V. S. / Small cationic DDA:TDB liposomes as protein vaccine adjuvants obviate the need for TLR agonists in inducing cellular and humoral responses. In: PLOS One. 2012 ; Vol. 7, No. 3.
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Small cationic DDA:TDB liposomes as protein vaccine adjuvants obviate the need for TLR agonists in inducing cellular and humoral responses. / Milicic, Anita; Kaur, Randip; Reyes-Sandoval, Arturo; Tang, Choon-Kit; Honeycutt, Jared; Perrie, Yvonne; Hill, Adrian V. S.

In: PLOS One, Vol. 7, No. 3, e34255, 2012.

Research output: Contribution to journalArticle

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AU - Milicic, Anita

AU - Kaur, Randip

AU - Reyes-Sandoval, Arturo

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