Target intelligence / Profile preview

Innate immune system pattern recognition pathways (AS03-mediated)

Molecular classification
Biological Pathway, Innate Immune System
01

Overview

AS03 (Adjuvant System 03) is a clinical-grade oil-in-water emulsion adjuvant composed of squalene, alpha-tocopherol (Vitamin E), and polysorbate 80, primarily used to enhance the efficacy of pandemic influenza vaccines (Morel et al., 2011; GSK). Unlike many traditional adjuvants that directly target specific pattern recognition receptors (PRRs) such as Toll-like receptors, AS03 functions by creating a localized immunocompetent environment at the injection site (Gueriaud et al., 2022). This process involves the rapid recruitment of innate immune cells, including monocytes and dendritic cells, and the induction of a specific cytokine profile characterized by IL-6 and CCL2 (Morel et al., 2011). A critical molecular mechanism of AS03 is the activation of the endoplasmic reticulum (ER) stress response, specifically the PERK-eIF2α pathway, which has been shown to be essential for its ability to boost the magnitude and breadth of the antibody response (Pulendran, 2014). By modulating these innate pathways, AS03 allows for significant antigen dose-sparing and provides enhanced protection against drifting viral strains (GSK). This entry is marked as incorrect because the provided name describes a complex biological mechanism and the effect of a specific adjuvant system rather than a single therapeutic target molecule or receptor.

Other names
AS03 adjuvant effectAS03-induced innate immune activationAS03-mediated ER stress responseAdjuvant System 03 effect
02

Mechanism of action

AS03 induces a local transient innate immune response by stimulating the production of cytokines and recruiting inflammatory cells to the injection site and draining lymph nodes, while also activating the endoplasmic reticulum (ER) stress response pathway (PERK-eIF2α) to enhance adaptive immunity (Morel et al., 2011; Pulendran, 2014).

03

Biological functions

Immune responseSignal transductionCytokine productionCell recruitmentEndoplasmic reticulum stress response
04

Disease associations

InfectionInflammation
05

Safety considerations

Injection site painSystemic reactogenicity (fever, malaise, myalgia)Historical association with narcolepsy in specific H1N1 vaccine formulations (Ahmed et al., 2014)
06

Interacting drugs

AS03

3 more in the full profile.

07

Biomarkers

Interleukin-6 (IL-6)C-X-C motif chemokine ligand 10 (CXCL10)C-C motif chemokine ligand 2 (CCL2)Phosphorylated eIF2αC-reactive protein (CRP)

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