Innate immune cells and receptors activated by oil-in-water adjuvants

Innate immune cells and receptors activated by oil-in-water (O/W) adjuvants represent a complex network of biological components that mediate the enhanced immunogenicity of modern vaccines. These adjuvants, typically squalene-based emulsions like MF59 and AS03, do not target a single receptor but instead trigger a 'danger signal' at the injection site that mimics an early infection (O'Hagan et al., Nature Reviews Drug Discovery, 2012). This process involves the rapid recruitment of various innate cells, including monocytes, macrophages, and neutrophils, and the activation of intracellular pathways such as the NLRP3 inflammasome (Ellebedy et al., Scientific Reports, 2011). By stimulating these innate components, O/W adjuvants facilitate more efficient antigen transport to draining lymph nodes and promote the differentiation of high-affinity T and B cells. The signaling often relies on the MyD88 adapter protein, even in the absence of direct Toll-like receptor (TLR) binding, highlighting a unique mechanism of action compared to traditional alum-based adjuvants (Morel et al., Vaccine, 2011). Understanding this system is crucial for the development of effective vaccines against infectious diseases like influenza and emerging viral threats, as it allows for dose-sparing and broader cross-reactivity.

Other names

Squalene-based adjuvant targetsMF59-responsive pathwaysAS03-responsive pathwaysO/W adjuvant-induced innate signalingEmulsion adjuvant targets

Oil-in-water adjuvants act by creating a local immunocompetent environment at the injection site, inducing the secretion of chemokines (e.g., CCL2, CXCL8) that recruit innate immune cells such as monocytes and neutrophils. These adjuvants often activate the NLRP3 inflammasome and utilize MyD88-dependent signaling pathways to enhance the uptake of vaccine antigens by professional antigen-presenting cells, ultimately boosting the adaptive immune response.