2020
DOI: 10.7554/elife.52687
|View full text |Cite
|
Sign up to set email alerts
|

Squalene emulsion-based vaccine adjuvants stimulate CD8 T cell, but not antibody responses, through a RIPK3-dependent pathway

Abstract: 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 tri… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1

Citation Types

0
37
0
1

Year Published

2021
2021
2025
2025

Publication Types

Select...
7

Relationship

1
6

Authors

Journals

citations
Cited by 57 publications
(42 citation statements)
references
References 78 publications
0
37
0
1
Order By: Relevance
“…Given the similarity of AS03 and MF59 both being squalene-based adjuvants, it is likely that they engage common pathways of innate immune activation. As described, both adjuvants stimulate innate cytokines and chemokines, but the extent to which they both depend on the IRE1α and RIPK3-dependent pathways 76 remains to be determined.…”
Section: Adjuvants In Licensed Vaccinesmentioning
confidence: 95%
See 3 more Smart Citations
“…Given the similarity of AS03 and MF59 both being squalene-based adjuvants, it is likely that they engage common pathways of innate immune activation. As described, both adjuvants stimulate innate cytokines and chemokines, but the extent to which they both depend on the IRE1α and RIPK3-dependent pathways 76 remains to be determined.…”
Section: Adjuvants In Licensed Vaccinesmentioning
confidence: 95%
“…Interestingly, and consistent with the study by Seubert et al, the response was intact in Nlrp3 -knockout and Casp1 -knockout mice 75 , which led the authors to conclude that MF59-adjuvanted vaccines induce antibody responses via an ASC-dependent, but inflammasome-independent, pathway. Finally, our recent work demonstrates that subcutaneous immunization of mice with MF59 plus antigen stimulates antigen-specific CD8 + T cell responses (which are stimulated at very low magnitude in the draining lymph nodes, but can be detected at much higher frequencies in tissues such as the lung and liver), via a mechanism dependent on receptor-interacting serine/threonine protein kinase 3 (RIPK3), which is a key mediator of necroptosis 76 . Thus, immunization of mice with antigen mixed with MF59 or its mimetic Addavax, but not with alum, induced rapid RIPK3-dependent necroptosis of lymph node macrophages.…”
Section: Adjuvants In Licensed Vaccinesmentioning
confidence: 99%
See 2 more Smart Citations
“… Immunocompetent environment induced by squalene-based emulsion (SE) adjuvants at the injection site. SE adjuvants cause local muscle cell damage (e.g., cell lysis by detergent-like molecules in the formulation), inducing the transient release of damage-associated molecular pattern (DAMP) signals such as ATP and double-stranded DNA, and the change in expression of as many as 891 genes in mice, compared to 312 genes by Alum at the injection site [ 35 , 42 , 43 , 44 ]. These DAMP signals bind to receptors on antigen-presenting cells (APCs) cells, trigger cytokine and chemokine secretion cascades as early as 3–6 h post-injection in mice [ 45 ].…”
Section: Se Adjuvants Induce An ‘Immunocompetent Environment’ Leadmentioning
confidence: 99%