Cationic pH-sensitive liposomes as tuberculosis subunit vaccine delivery systems: Effect of liposome composition on cellular innate immune responses

•Cationic pH-sensitive liposomes are effectively taken up by dendritic cells (DCs)•1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC) improves DC activation.•EPC-based pH-sensitive liposomes effectively induce activation of DCs.•pH-sensitive liposomes trigger antigen-specific IFNγ production in T-c...

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Veröffentlicht in:International immunopharmacology Jg. 145; S. 113782
Hauptverfasser: Szachniewicz, M.M., Meijgaarden, K.E. van, Kavrik, E., Jiskoot, W., Bouwstra, J.A., Haks, M.C., Geluk, A., Ottenhoff, T.H.M.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Netherlands Elsevier B.V 03.01.2025
Schlagworte:
Adjuvant
Animals
Antigens, Bacterial - immunology
Cationic liposome
Cations
CD8-Positive T-Lymphocytes - immunology
Cells, Cultured
Cytokines - metabolism
Dendritic cells
Dendritic Cells - immunology
Humans
Hydrogen-Ion Concentration
Immunity, Cellular
Immunity, Innate
Immunogenicity
Liposomes
Mycobacterium tuberculosis - immunology
pH-sensitive liposome
Tuberculosis
Tuberculosis - immunology
Tuberculosis - prevention & control
Tuberculosis Vaccines - administration & dosage
Tuberculosis Vaccines - immunology
Vaccines, Subunit - administration & dosage
Vaccines, Subunit - immunology
CXCL
PPD
Cationic liposome
MHC
TNF
IFN
PDI
GM-CSF
FBS
CCR7
Adjuvant
TLR
Th1
DOPC
DOPE
CD
PE-Cy5
DOBAQ
Dendritic cells
BCG
MACS
IQR
M−CSF
CCL
PBMC
AER
TB
PAMP
MDDC
Tuberculosis
APC
Immunogenicity
PE
LAL
CHEMS
EPC
Mtb
DOTAP
HLA
Ig
PCR
pH-sensitive liposome
DC
ISSN:1567-5769, 1878-1705, 1878-1705
Online-Zugang:Volltext
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Zusammenfassung:•Cationic pH-sensitive liposomes are effectively taken up by dendritic cells (DCs)•1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC) improves DC activation.•EPC-based pH-sensitive liposomes effectively induce activation of DCs.•pH-sensitive liposomes trigger antigen-specific IFNγ production in T-cells.•pH-sensitive liposomes are promising tuberculosis vaccine delivery candidates. Tuberculosis (TB) is a major global health problem, and the development of effective and safe vaccines is urgently needed. CD8+ T-cells play an important role alongside CD4+ T-cells in the protective immune response against TB. pH-sensitive liposomes are hypothesized to boost CD8+ T-cell responses by promoting class I presentation through a mechanism involving pH-dependent endosomal escape and the cytosolic transfer of antigens. The aim of the study was to explore the potential of pH-sensitive liposomes as a novel delivery system for a multi-stage protein subunit vaccine against TB in primary human cells. The liposomes were formulated with the fusion antigen Ag85b-ESAT6-Rv2034 (AER), which was previously shown to be effective in reducing bacterial load in the lungs HLA-DR3 transgenic mice and guinea pigs. The liposomes were assessed in vitro for cellular uptake, cell viability, upregulation of cell surface activation markers, induction of cytokine production using human monocyte-derived dendritic cells (MDDCs), and activation of human antigen-specific T-cells. Liposome DOPC:DOPE:DOBAQ:EPC (3:5:2:4 M ratio) was effectively taken up, induced several cell surface activation markers, and production of CCl3, CCL4, and TNFα in MDDCs. It also induced upregulation of CD154 and IFNγ in T-cell clones in an antigen-specific manner. Thus, cationic pH-sensitive liposome-based TB vaccines have been demonstrated to be capable of inducing robust protective Mtb-specific immune responses, positioning them as promising candidates for effectiveTBvaccination.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1567-5769
1878-1705
1878-1705
DOI:10.1016/j.intimp.2024.113782