Intrinsic immunogenicity of liposomes for tuberculosis vaccines: Effect of cationic lipid and cholesterol

Tuberculosis (TB) is still among the deadliest infectious diseases, hence there is a pressing need for more effective TB vaccines. Cationic liposome subunit vaccines are excellent vaccine candidates offering effective protection with a better safety profile than live vaccines. In this study, we aim...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences Vol. 195; p. 106730
Main Authors: Szachniewicz, M.M., Neustrup, M.A., van Meijgaarden, K.E., Jiskoot, W., Bouwstra, J.A., Haks, M.C., Geluk, A., Ottenhoff, T.H.M.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.04.2024
Subjects:
Adjuvant
Adjuvants, Immunologic - chemistry
Animals
Cationic liposome
Cholesterol
Cholesterol - chemistry
Dendritic cells
Humans
Immunogenicity
Lipids - chemistry
Liposomes - chemistry
Mice
Mice, Inbred C57BL
Tuberculosis
Tuberculosis Vaccines - chemistry
Vaccines
Vaccines, Subunit
DDA
CXCL
M-CSF
DC-cholesterol
Cationic liposome
TNF
DODMA
SA
IFN
PDI
GM-CSF
FBS
Adjuvant
CCR7
Th1
DOPC
CD
DSPC
GL-67
Dendritic cells
BCG
MACS
IQR
CCL
PBMC
Cholesterol
AER
TB
PAMP
MDDC
Tuberculosis
Immunogenicity
APC
MVL5
EPC
Mtb
DOTAP
HLA
Ig
DC
ISSN:0928-0987, 1879-0720, 1879-0720
Online Access:Get full text
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Summary:Tuberculosis (TB) is still among the deadliest infectious diseases, hence there is a pressing need for more effective TB vaccines. Cationic liposome subunit vaccines are excellent vaccine candidates offering effective protection with a better safety profile than live vaccines. In this study, we aim to explore intrinsic adjuvant properties of cationic liposomes to maximize immune activation while minimizing aspecific cytotoxicity. To achieve this, we developed a rational strategy to select liposomal formulation compositions and assessed their physicochemical and immunological properties in vitro models using human monocyte-derived dendritic cells (MDDCs). A broad selection of commercially available cationic compounds was tested to prepare liposomes containing Ag85B-ESAT6-Rv2034 (AER) fusion protein antigen. 1,2-Dioleoyl-sn‑glycero-3-ethylphosphocholine (EPC)-based liposomes exhibited the most advantageous activation profile in MDDCs as assessed by cell surface activation markers, cellular uptake, antigen-specific T-cell activation, cytokine production, and cellular viability. The addition of cholesterol to 20 mol% improved the performance of the tested formulations compared to those without it; however, when its concentration was doubled there was no further benefit, resulting in reduced cell viability. This study provides new insights into the role of cationic lipids and cholesterol in liposomal subunit vaccines. [Display omitted]
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ISSN:0928-0987
1879-0720
1879-0720
DOI:10.1016/j.ejps.2024.106730