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

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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 - 1 Mar 2015

Keywords

  • adjuvants, immunologic
  • animals
  • bacterial proteins
  • cytokines
  • female
  • glycolipids
  • immunity, cellular
  • immunoglobulins
  • liposomes
  • mice, inbred C57BL
  • multivariate analysis
  • mycobacterium tuberculosis
  • phosphatidylcholines
  • quaternary ammonium compounds
  • vaccines

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