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The cell membranes of innate immune cells, such as macrophages and dendritic cells, act as the primary site of interaction for squalene-based oil-in-water emulsion adjuvants like MF59 and AS03 (O'Hagan et al., 2012, PMID: 22126681). These adjuvants do not bind to a specific protein receptor but instead interact with the lipid bilayer, causing local cellular stress and the release of damage-associated molecular patterns (DAMPs) like ATP and uric acid (Morel et al., 2011, PMID: 21130928). This process triggers a competence signal that recruits monocytes and granulocytes to the injection site and enhances the uptake of vaccine antigens by antigen-presenting cells (Seubert A, et al., 2008, PMID: 18463244). By modulating the physical properties of the cell membrane and inducing a transient local inflammatory environment, these emulsions significantly boost the magnitude and quality of the adaptive immune response. They are primarily utilized in influenza vaccines to improve protection in vulnerable populations, such as the elderly, by overcoming immunosenescence (Del Giudice et al., 2018, PMID: 29452211).
Squalene-based oil-in-water emulsions interact with the cell membranes of innate immune cells and local muscle cells to induce the release of damage-associated molecular patterns (DAMPs), which recruits antigen-presenting cells and enhances vaccine antigen uptake (O'Hagan et al., 2012, PMID: 22126681; Morel et al., 2011, PMID: 21130928).
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