New chimeric TLR7/NOD2 agonist is a potent adjuvant to induce mucosal immune responses

EBioMedicine

卷:58

Fabienne Vernejoul¹  Thierry Lioux²  Laura Papagno³  Nicolas Rochereau⁴  Stéphane Paul⁴  Victor Appay⁴  Bernard Verrier⁵  Alice Gutjahr⁵  Blandine Chanut⁵  Eric Perouzel⁵  Fabienne Jospin⁶ 

[1] Groupe Immunité des Muqueuses et Agents Pathogènes, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique en Vaccinologie 1408, Faculté de Médecine de Saint-Etienne, Saint-Etienne, France;

[2] INSERM U1135, CIMI-Paris, Paris, France;

[3] Laboratoire de Biologie Tissulaire et d'Ingénierie Thérapeutique, Unité Mixte de Recherche 5305, Université Lyon 1, Centre National de la Recherche Scientifique (CNRS), Lyon, France;

[4] InvivoGen, 5 Rue Jean Rodier F-31400, Toulouse, France;

[5] Sorbonne Universités, UPMC Univ Paris 06, DHU FAST, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France;

关键词: Adjuvants;    TLR7;    NOD2;    Vaccine;    Chimeric;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: PRR (Pattern Recognition Receptor) agonists have been widely tested as potent vaccine adjuvants. TLR7 (Toll-Like Receptor 7) and NOD2 (nucleotide-binding oligomerization domain 2) are key innate receptors widely expressed at mucosal levels. Methods: Here, we evaluated the immunostimulatory properties of a novel hybrid chemical compound designed to stimulate both TLR7 and NOD2 receptors. Finding: The combined TLR7/NOD2 agonist showed increase efficacy than TLR7L or NOD2L agonists alone or combined in different in vitro models. Dual TLR7/NOD2 agonist efficiently stimulates TLR7 and NOD2, and promotes the maturation and reprogramming of human dendritic cells, as well as the secretion of pro-inflammatory or adaptive cytokines. This molecule also strongly induces autophagy in human cells which is a major intracellular degradation system that delivers cytoplasmic constituents to lysosomes in both MHC class I and II-restricted antigen presentation. In vivo, TLR7/NOD2L agonist is a potent adjuvant after intranasal administration with NP-p24 HIV vaccine, inducing high-quality humoral and adaptive responses both in systemic and mucosal compartments. Use of TLR7/NOD2L adjuvant improves very significantly the protection of mice against an intranasal challenge with a vaccinia virus expressing the p24. Interpretation: Dual TLR7/NOD2L agonist is a very potent and versatile vaccine adjuvant and promote very efficiently both systemic and mucosal immunity. Funding: This work was supported by Sidaction.

【 授权许可】

Unknown