Covalently Conjugated NOD2/TLR7 Agonists Are Potent and Versatile Immune Potentiators
| Autor: | Samo Guzelj, Matjaž Weiss, Bram Slütter, Ruža Frkanec, Žiga Jakopin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Immunity
Cellular synthesis of NOD2 agonist udc:615.371:616-097 cepiva pattern recognition receptors Nod2 Signaling Adaptor Protein immunostimulatory activity vaccines NOD2 • TLR7 • Adjuvant • Vaccine • Conjugate imunostimulatorna aktivnost immune responses Toll-like receptor 7 receptor TLR7 Mice Toll-Like Receptor 7 Adjuvants Immunologic receptorji za prepoznavanje vzorcev Drug Discovery Leukocytes Mononuclear sinteza agonista NOD2 Molecular Medicine Humans Animals imunski odziv Immunization |
| Zdroj: | Journal of medicinal chemistry, vol. 65, no. 22, 2022. |
| ISSN: | 1520-4804 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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