Covalently conjugated NOD2/TLR7 agonists are potent and versatile immune potentiatorsGuzelj, Samo (Avtor) Weiss, Matjaž (Avtor) Slütter, Bram (Avtor) Frkanec, Ruža (Avtor) Jakopin, Žiga (Avtor) immunostimulatory activityvaccinesimmune responsespattern recognition receptorssynthesis of NOD2 agonistToll-like receptor 7The success of vaccination with subunit vaccines often relies on the careful choice of adjuvants. There is great interest in developing new adjuvants that can elicit a cellular immune response. Here, we address this challenge by taking advantage of the synergistic cross-talk between two pattern recognition receptors: nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) and Toll-like receptor 7 (TLR7). We designed two conjugated NOD2/TLR7 agonists, which showed potent immunostimulatory activities in human primary peripheral blood mononuclear cells and murine bone-marrow-derived dendritic cells. One of these, 4, also generated a strong antigen-specific immune response in vivo, with a Th1-polarized profile. Importantly, our study shows that novel NOD2/TLR7 agonists elicit sophisticated and fine-tuned immune responses that are inaccessible to individual NOD2 and TLR7 agonists.20222022-12-09 07:41:23Članek v reviji143233UDK: 615.371:616-097ISSN pri članku: 1520-4804DOI: 10.1021/acs.jmedchem.2c00808COBISS_ID: 128189187sl