Pattern recognition receptors and innate immune pathways activated by Advax adjuvant

Advax is a unique vaccine adjuvant based on delta-inulin microparticles that enhances both humoral and cellular immune responses without the high levels of inflammation typical of other adjuvants (Petrovsky & Cooper, 2015). Unlike traditional adjuvants that target Toll-like receptors (TLRs) or the NLRP3 inflammasome, Advax primarily functions through the activation of the alternative complement pathway and interactions with C-type lectin receptors on antigen-presenting cells (Honda-Okubo et al., 2021). This activation results in the deposition of complement component C3d on the vaccine antigen, which facilitates its recognition by Complement Receptor 2 (CR2) on B cells, thereby lowering the activation threshold and promoting affinity maturation (Sajkov et al., 2014). Advax is characterized by its ability to amplify the inherent immune bias of the co-administered antigen, making it a versatile and safe platform for various vaccines, including those for influenza, hepatitis B, and COVID-19. Its non-inflammatory profile makes it particularly suitable for populations sensitive to reactogenic adjuvants, such as the elderly and children (Petrovsky & Cooper, 2015). Research indicates that Advax does not directly activate the NF-κB pathway, which contributes to its excellent tolerability in clinical settings (Petrovsky & Cooper, 2015). The adjuvant has demonstrated efficacy in enhancing protection against a broad range of viral, bacterial, and parasitic pathogens in preclinical and clinical studies (Honda-Okubo et al., 2023).

Other names

Advax mechanism of actionDelta-inulin signaling pathwaysAlternative complement pathway activation by AdvaxC-type lectin receptor activation by Advax

Advax (delta-inulin) enhances vaccine immunogenicity by activating the alternative complement pathway and potentially interacting with C-type lectin receptors (e.g., DC-SIGN) on antigen-presenting cells (Petrovsky & Cooper, 2015). This leads to C3d deposition on antigens, which then binds to Complement Receptor 2 (CR2) on B cells and follicular dendritic cells, lowering the threshold for B-cell activation and enhancing antigen presentation without inducing typical pro-inflammatory PRR signaling (e.g., TLRs or NF-κB) (Honda-Okubo et al., 2021).