Target intelligence / Profile preview

Squalene-based emulsion adjuvant-mediated immune activation (null)

Target
null
Molecular classification
Other (adjuvant formulation/mechanism, not a molecular target)
01

Overview

Squalene-based emulsion adjuvants, such as MF59 and AS03, are oil-in-water formulations used in vaccines to boost immune responses. They function by enhancing antigen uptake and presentation by local innate immune cells (dendritic cells, monocytes, macrophages), increasing recruitment of immune cells to the injection site and draining lymph nodes, and stimulating local cytokine production. This results in a stronger and broader adaptive immune response, notably improved antibody and CD8 T cell responses, compared to non-adjuvanted vaccines. The action involves RIPK3-dependent necroptosis of lymph node-resident macrophages for CD8 T cell activation and diverse pathways for antibody enhancement. Squalene adjuvants have an extensive safety record in seasonal and pandemic influenza vaccines and are being applied to new vaccine candidates, including for COVID-19, especially where strong or broader immune responses are needed[1][2][3][4][5][6][7].

Other names
Squalene emulsion adjuvantoil-in-water emulsion adjuvantMF59AS03
02

Mechanism of action

Enhancement of antigen uptake and presentation by dendritic cells (DCs), monocytes, and macrophages Recruitment of neutrophils, monocytes, and other granulocytes to the injection site and draining lymph nodes Activation of local cytokine and chemokine responses Promotion of cross-presentation to CD8 T cells via RIPK3-dependent necroptosis of lymph node-resident macrophages Depot formation (sustained antigen release)[1][2][3][4][5][6][7]

03

Biological functions

Immune responseAntigen presentation enhancementVaccine adjuvant activityRecruitment and activation of innate immune cells
04

Disease associations

Infection (vaccination against viral and bacterial pathogens)Other (improving immunogenicity in elderly or immunocompromised populations)
05

Safety considerations

Local reactogenicity (swelling, pain at the injection site)Rare associations with autoimmune or hypersensitivity reactions (e.g. the narcolepsy signal with AS03-adjuvanted influenza vaccines, though evidence remains inconclusive)[6]General safety supported by large-scale use, but vigilance for rare events is required
06

Interacting drugs

Squalene-based emulsion adjuvants such as MF59 (used in influenza vaccines)

3 more in the full profile.

07

Biomarkers

Increased serum cytokines such as IL-6, TNF, IFN-γ, IL-18 after vaccination[1][5]Elevated numbers of activated dendritic cells and monocytes at the injection site and draining lymph nodes[6]Induction of uric acid as a danger-associated molecular pattern (DAMP)[7]

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