Emerging evidences indicate that activation of immune cells through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) or NOD-like receptors (NLRs) may be critical mechanisms. Most of the adjuvants used in clinical trials target TLRs, but their usefulness in conjunction with NLRs agonists remains poorly studied.
In this study, we evaluate a chimeric ligand that targets both TLR2 and NOD2 receptors. We assessed its ability to enhance monocyte-derived dendritic cells (MoDCs) maturation in vitro and its effect on systemic and mucosal immune responses in mice.
In vitro, we showed that the chimeric ligand upregulated the expression of MoDCs maturation markers, of costimulatory molecules, and of proinflammatory cytokines.
Furthermore, in vivo analysis revealed that its coadministration with biodegradable nanoparticles carrying Gag p24 HIV-1 antigen induced high antigen-specific IgA and IgG titers at both systemic and mucosal sites after parenteral immunizations.
These findings demonstrate the potential of chimeric molecules TLR/NOD as adjuvants for vaccines to induce systemic and mucosal immune responses.