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Innate immune system components modulated by MF59 refer to a diverse set of proteins and cellular pathways activated by the squalene-based oil-in-water emulsion adjuvant MF59. Unlike many other adjuvants, MF59 does not primarily target Toll-like receptors (TLRs) but instead induces a local "immunocompetent environment" by stimulating the release of chemokines such as CCL2, CCL3, and CXCL8, which recruit monocytes, macrophages, and dendritic cells to the site of injection (O'Hagan et al., 2012; Seubert et al., 2008). It also triggers the release of endogenous danger signals like ATP and activates the NLRP3 inflammasome, leading to the maturation of pro-inflammatory cytokines like IL-1 beta and IL-18 (Vono et al., 2013; Ellebedy et al., 2011). These actions collectively enhance the recruitment of antigen-presenting cells, improve antigen uptake, and facilitate the transport of antigens to draining lymph nodes, thereby significantly boosting the adaptive immune response to vaccine antigens. MF59 is widely used in influenza vaccines, particularly for elderly populations, to overcome immunosenescence and provide broader protection (Schultze et al., 2008). The modulation of these innate components is characterized by a MyD88-independent pathway, distinguishing it from TLR-dependent adjuvants.
MF59 acts as an adjuvant by creating a local "immunocompetent environment" at the injection site, stimulating the production of chemokines (e.g., CCL2, CXCL8) and cytokines, and activating the NLRP3 inflammasome to enhance antigen uptake and transport to lymph nodes.
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