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The innate immune pathways activated by AS03 (Adjuvant System 03) represent a coordinated series of molecular and cellular events that enhance the immunogenicity of vaccines (Morel et al., 2011). AS03 is an oil-in-water emulsion composed of squalene, DL-α-tocopherol (vitamin E), and polysorbate 80, primarily utilized in pandemic influenza vaccines to boost antibody responses (Givestein et al., 2016). Its mechanism of action involves the induction of a transient, localized innate immune response at the injection site and draining lymph nodes, characterized by the activation of the endoplasmic reticulum (ER) stress response and the NF-κB signaling pathway (Morel et al., 2011). This activation leads to the rapid production of key chemokines, such as CCL2 (MCP-1) and CXCL10 (IP-10), which facilitate the recruitment of inflammatory cells, including monocytes and dendritic cells (Garçon et al., 2012). These recruited cells are essential for efficient antigen uptake, processing, and transport to the lymph nodes, ultimately promoting a robust and long-lasting adaptive immune response (Cohet et al., 2019). By modulating these innate pathways, AS03 significantly increases the magnitude and breadth of the immune response, providing enhanced protection against diverse viral strains (Givestein et al., 2016).
AS03 triggers a transient local innate immune response by activating the endoplasmic reticulum (ER) stress response and NF-κB pathway, leading to the secretion of chemokines like CCL2 and CXCL10 that recruit antigen-presenting cells (Morel et al., 2011; Givestein et al., 2016).
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