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Innate immune cells at the injection site and draining lymph nodes represent the primary cellular targets for oil-in-water (O/W) vaccine adjuvants such as MF59 and AS03. Upon administration, these squalene-based emulsions trigger a rapid 'danger signal' or 'immunocompetent environment' characterized by the release of chemokines and cytokines from resident cells (Seubert et al., 2008, Journal of Immunology). This signaling cascade recruits various innate populations, including monocytes, neutrophils, and dendritic cells, to the site of injection. These recruited cells are essential for the efficient uptake of vaccine antigens and their subsequent transport to the draining lymph nodes. In the lymph nodes, these activated innate cells differentiate into professional antigen-presenting cells that bridge the gap between innate and adaptive immunity, ultimately enhancing the magnitude and quality of the antibody response (O'Hagan et al., 2012, Nature Reviews Drug Discovery). While highly effective for increasing vaccine potency, particularly in elderly or pediatric populations, the activation of these cells is also responsible for common reactogenicity symptoms like local inflammation and soreness.
Oil-in-water adjuvants act by creating a local 'immunocompetent environment' at the injection site, inducing the secretion of chemokines (e.g., CCL2, CCL3, CXCL8) that recruit monocytes, neutrophils, and dendritic cells. These cells internalize the vaccine antigen and transport it to the draining lymph nodes, where they mature and facilitate the activation of T and B cells (O'Hagan et al., 2012, Vaccine; Garçon et al., 2012, Expert Review of Vaccines).
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