Naslov
Covalently Conjugated NOD2/TLR7 Agonists Are Potent and Versatile Immune Potentiators

Autori
Guzelj, Samo ; Weiss, Matjaž ; Slütter, Bram ; Frkanec, Ruža ; Jakopin, Žiga

Izvornik
Journal of medicinal chemistry (0022-2623) 65 (2022), 22; 15085-15101

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
NOD2 • TLR7 • Adjuvant • Vaccine • Conjugate

Sažetak
The 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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

POVEZANOST RADA