Innate immune receptors and pathways engaged by AS03 adjuvant (AS03)

AS03 (Adjuvant System 03) is a clinical-grade oil-in-water emulsion adjuvant consisting of squalene, DL-α-tocopherol (Vitamin E), and polysorbate 80. Unlike many traditional adjuvants that target specific pattern recognition receptors (PRRs) like Toll-like receptors (TLRs), AS03 acts through a more complex engagement of innate immune pathways, including the activation of the NF-κB transcription factor and the induction of the endoplasmic reticulum (ER) stress response (Morel et al., 2011, Nature Medicine; Givens et al., 2021, Journal of Immunology). This activation results in a transient, localized production of cytokines and chemokines such as IL-6, CCL2, and CXCL10 at the injection site and draining lymph nodes (Garçon et al., 2012, Expert Review of Vaccines). These signals facilitate the recruitment of inflammatory monocytes and the activation of dendritic cells, which are essential for the efficient priming of the adaptive immune system (Burny et al., 2017, Clinical and Vaccine Immunology). The inclusion of α-tocopherol is a defining feature of AS03, as it significantly enhances the magnitude of the innate response and the subsequent production of high-affinity antibodies compared to squalene-only emulsions (Morel et al., 2011). AS03 has been successfully utilized in pandemic influenza vaccines (e.g., Pandemrix) and COVID-19 vaccines (e.g., VidPrevtyn Beta) to achieve dose-sparing and broader cross-reactivity (Cooch et al., 2013, Vaccine).

Other names

AS03-responsive innate immune signalingAS03-induced inflammatory pathwaysAS03-mediated immune activation

AS03 triggers a local innate immune response by activating the NF-κB pathway and inducing endoplasmic reticulum (ER) stress, leading to the secretion of cytokines and chemokines that recruit and activate antigen-presenting cells.