Squalene emulsion-based vaccine adjuvants stimulate CD8 T cell, but not antibody responses, through a RIPK3-dependent pathway.
Adjuvants, Immunologic
Animals
Antibody Formation
Basic-Leucine Zipper Transcription Factors
/ metabolism
CD8-Positive T-Lymphocytes
/ immunology
Emulsions
Immunity, Innate
Lymph Nodes
/ cytology
Macrophages
/ immunology
Mice
Mice, Inbred C57BL
Polysorbates
Receptor-Interacting Protein Serine-Threonine Kinases
/ metabolism
Repressor Proteins
/ metabolism
Squalene
/ immunology
MF59
RIPK3
adjuvant
cell death
immunology
inflammation
macrophage
mouse
vaccine
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
09 06 2020
09 06 2020
Historique:
received:
12
10
2019
accepted:
08
06
2020
pubmed:
10
6
2020
medline:
4
3
2021
entrez:
10
6
2020
Statut:
epublish
Résumé
The squalene-based oil-in-water emulsion (SE) vaccine adjuvant MF59 has been administered to more than 100 million people in more than 30 countries, in both seasonal and pandemic influenza vaccines. Despite its wide use and efficacy, its mechanisms of action remain unclear. In this study we demonstrate that immunization of mice with MF59 or its mimetic AddaVax (AV) plus soluble antigen results in robust antigen-specific antibody and CD8 T cell responses in lymph nodes and non-lymphoid tissues. Immunization triggered rapid RIPK3-kinase dependent necroptosis in the lymph node which peaked at 6 hr, followed by a sequential wave of apoptosis. Immunization with alum plus antigen did not induce RIPK3-dependent signaling. RIPK3-dependent signaling induced by MF59 or AV was essential for cross-presentation of antigen to CD8 T cells by Batf3-dependent CD8
Identifiants
pubmed: 32515732
doi: 10.7554/eLife.52687
pii: 52687
pmc: PMC7314549
doi:
pii:
Substances chimiques
Addavax
0
Adjuvants, Immunologic
0
Basic-Leucine Zipper Transcription Factors
0
Emulsions
0
MF59 oil emulsion
0
Polysorbates
0
Repressor Proteins
0
SNFT protein, mouse
0
Squalene
7QWM220FJH
Receptor-Interacting Protein Serine-Threonine Kinases
EC 2.7.11.1
Ripk3 protein, mouse
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R37 AI048638
Pays : United States
Organisme : NIAID NIH HHS
ID : R38 AI140299
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI090023
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI057266
Pays : United States
Organisme : NIDDK NIH HHS
ID : R37 DK057665
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000454
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR025679
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI048638
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI020211
Pays : United States
Informations de copyright
© 2020, Kim et al.
Déclaration de conflit d'intérêts
EK, MW, LG, BM, SL, PM, MC, MN, RR, HM, MM, AG, EM, JJ, BP No competing interests declared
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