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

Tools

Kastner, Elisabeth and Hussain, M. Jubair and Bramwell, Vincent W. and Christensen, Dennis and Perrie, Yvonne (2015) Correlating liposomal adjuvant characteristics to in-vivo cell-mediated immunity using a novel Mycobacterium tuberculosis fusion protein : a multivariate analysis study. Journal of Pharmacy and Pharmacology, 67 (3). pp. 450-463. ISSN 0022-3573 (https://doi.org/10.1111/jphp.12390)

[thumbnail of Kastner-etal-JPP-2015-Correlating-liposomal-adjuvant-characteristics-to-in-vivo-cell-mediated]
Preview
 Text. Filename: Kastner_etal_JPP_2015_Correlating_liposomal_adjuvant_characteristics_to_in_vivo_cell_mediated.pdf
Accepted Author Manuscript
Download (547kB)| Preview

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.

CORE (COnnecting REpositories)