Innate immune pathways activated by AS03B adjuvant (AS03-activated pathways)

AS03 (Adjuvant System 03) is a clinical-grade oil-in-water emulsion adjuvant consisting of squalene, alpha-tocopherol (Vitamin E), and polysorbate 80, primarily used in pandemic influenza vaccines. The innate immune pathways activated by AS03B (a specific dose formulation) involve the rapid, transient induction of cytokines and chemokines such as IL-6, CCL2, and CXCL10 at the injection site and draining lymph nodes (Morel et al., 2011, Vaccine). Unlike other squalene-based emulsions, AS03's activity is uniquely dependent on alpha-tocopherol, which triggers an endoplasmic reticulum (ER) stress response and the unfolded protein response (UPR) (Morel et al., 2011, Vaccine). This signaling cascade leads to the recruitment and activation of antigen-presenting cells, particularly monocytes and dendritic cells, which subsequently enhance the magnitude and breadth of the adaptive immune response (Garçon et al., 2012, Expert Review of Vaccines). While highly effective in pandemic influenza vaccines like Pandemrix, the pathways activated by AS03 have been scrutinized due to a historical association between specific AS03-adjuvanted vaccines and an increased risk of narcolepsy in certain populations (Partinen et al., 2012, PLoS ONE).

Other names

AS03-induced innate responseAS03 signaling cascadeAdjuvant System 03-mediated activationAS03-triggered immune pathways

Induction of local innate immune response via endoplasmic reticulum stress and cytokine/chemokine production