Correlating liposomal adjuvant characteristics to in-vivo cell-mediated immunity using a novel Mycobacterium tuberculosis fusion protein: a multivariate analysis study

Elisabeth Kastner, M. Jubair Hussain, Vincent W. Bramwell, Dennis Christensen, Yvonne Perrie*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Objective In this study, we have used a chemometrics-based method to correlate key liposomal adjuvant attributes with in-vivo immune responses based on multivariate analysis. Methods The liposomal adjuvant composed of the cationic lipid dimethyldioctadecylammonium bromide (DDA) and trehalose 6,6-dibehenate (TDB) was modified with 1,2-distearoyl-sn-glycero-3-phosphocholine at a range of mol% ratios, and the main liposomal characteristics (liposome size and zeta potential) was measured along with their immunological performance as an adjuvant for the novel, postexposure fusion tuberculosis vaccine, Ag85B-ESAT-6-Rv2660c (H56 vaccine). Partial least square regression analysis was applied to correlate and cluster liposomal adjuvants particle characteristics with in-vivo derived immunological performances (IgG, IgG1, IgG2b, spleen proliferation, IL-2, IL-5, IL-6, IL-10, IFN-γ). Key findings While a range of factors varied in the formulations, decreasing the 1,2-distearoyl-sn-glycero-3-phosphocholine content (and subsequent zeta potential) together built the strongest variables in the model. Enhanced DDA and TDB content (and subsequent zeta potential) stimulated a response skewed towards a cell mediated immunity, with the model identifying correlations with IFN-γ, IL-2 and IL-6. Conclusion This study demonstrates the application of chemometrics-based correlations and clustering, which can inform liposomal adjuvant design.

Original languageEnglish
Pages (from-to)450-463
Number of pages14
JournalJournal of Pharmacy and Pharmacology
Volume67
Issue number3
Early online date12 Feb 2015
DOIs
Publication statusPublished - 2015

Bibliographical note

Funding: EPSRC; and NewTBVAC (contract no. HEALTHF3-2009-241745)

Keywords

  • in-vivo correlation
  • liposome
  • multivariate analysis
  • subunit vaccine

Fingerprint Dive into the research topics of 'Correlating liposomal adjuvant characteristics to in-vivo cell-mediated immunity using a novel <i>Mycobacterium tuberculosis</i> fusion protein: a multivariate analysis study'. Together they form a unique fingerprint.

Cite this