A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity.
Adaptive Immunity
/ drug effects
Adjuvants, Immunologic
/ pharmacology
Animals
B-Lymphocytes
/ immunology
CD4-Positive T-Lymphocytes
/ immunology
Female
Lymph
/ drug effects
Macaca mulatta
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Nanoparticles
Rats
Rats, Wistar
Saponins
/ pharmacology
Toll-Like Receptors
/ agonists
Journal
Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624
Informations de publication
Date de publication:
03 Dec 2021
03 Dec 2021
Historique:
entrez:
3
12
2021
pubmed:
4
12
2021
medline:
9
3
2022
Statut:
ppublish
Résumé
Saponins are potent and safe vaccine adjuvants, but their mechanisms of action remain incompletely understood. Here, we explored the properties of several saponin formulations, including immune-stimulatory complexes (ISCOMs) formed by the self-assembly of saponin and phospholipids in the absence or presence of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). We found that MPLA self-assembles with saponins to form particles physically resembling ISCOMs, which we termed saponin/MPLA nanoparticles (SMNP). Saponin-containing adjuvants exhibited distinctive mechanisms of action, altering lymph flow in a mast cell–dependent manner and promoting antigen entry into draining lymph nodes. SMNP was particularly effective, exhibiting even greater potency than the compositionally related adjuvant AS01
Identifiants
pubmed: 34860581
doi: 10.1126/sciimmunol.abf1152
pmc: PMC8763571
mid: NIHMS1767963
doi:
Substances chimiques
Adjuvants, Immunologic
0
Saponins
0
Toll-Like Receptors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabf1152Subventions
Organisme : NIAID NIH HHS
ID : R01 AI153098
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007386
Pays : United States
Organisme : NIAID NIH HHS
ID : R61 AI161818
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI048240
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214913
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI104715
Pays : United States
Organisme : NIH HHS
ID : U42 OD011023
Pays : United States
Organisme : NIAID NIH HHS
ID : R61 AI161297
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137057
Pays : United States
Organisme : NIH HHS
ID : P51 OD011132
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI125068
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI125068
Pays : United States
Organisme : NIH HHS
ID : P51 OD011133
Pays : United States
Organisme : NIH HHS
ID : S10 OD021831
Pays : United States
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