title: Correlating liposomal adjuvant characteristics to in-vivo cell-mediated immunity using a novel Mycobacterium tuberculosis fusion protein: a multivariate analysis study.
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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  This study demonstrates the application of chemometrics-based correlations and clustering, which can inform liposomal adjuvant design.
authors: School of Life and Health Sciences, Aston University, Birmingham, UK.
authors: Elisabeth
authors: E
authors: Kastner
authors: M Jubair
authors: MJ
authors: Hussain
authors: Vincent W
authors: VW
authors: Bramwell
authors: Dennis
authors: D
authors: Christensen
authors: Yvonne
authors: Y
authors: Perrie
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006017:Glycolipids / Q000737:chemistry*; D007111:Immunity, Cellular; D007136:Immunoglobulins / Q000097:blood; D008081:Liposomes; D008810:Mice, Inbred C57BL; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D014612:Vaccines
chemical_list: D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D016207:Cytokines; D006017:Glycolipids; D007136:Immunoglobulins; D008081:Liposomes; D010713:Phosphatidylcholines; D000644:Quaternary Ammonium Compounds; D014612:Vaccines; C507803:trehalose 6,6'-dibehenate; C015831:dimethyldioctadecylammonium; C010942:1,2-distearoyllecithin
keywords: in-vivo correlation; liposome; multivariate analysis; subunit vaccine