TLR agonist(Decoy Biosystems)

Combinations of Toll-like receptor (TLR) agonists are being explored to alleviate systemic toxicity and achieve long-lasting desirable immune responses. In this study, we investigated the use of a triple-TLR agonists' combination (LPS, TLR4; R-848, TLR7 and CpG-ODN, TLR21) as an adjuvant with the inactivated Newcastle disease virus (NDV) vaccine in chickens. We assessed the immune response kinetics by stimulating chicken peripheral blood mononuclear cells (PBMCs) with the triple agonist combination and analyzing immune-related gene expression using quantitative PCR. Additionally, transcriptomic analysis was performed in spleen samples from birds injected with the triple TLR agonists. In the immunization study, birds were vaccinated with an inactivated NDV vaccine alone or in combination with different TLR agonist mixtures (single, dual, or triple), followed by assessment of both humoral and cellular immune responses and protection against challenge. Results from immune response study showed significant upregulation of IL-1β, IFN-γ, IL-4, IFN-β, iNOS and MHC-II transcripts, indicating the pro-inflammatory, anti-viral and mixed Th1/Th2 responses in triple TLR agonists' combination. Transcriptomic analysis revealed significant upregulation of 19 differentially expressed genes (DEGs) related to immune function in triple-TLR agonists signaling pathway such as pro-inflammatory, anti-inflammatory and anti-viral response. Furthermore, the immunization study demonstrated that the triple-TLR agonist combination, at a low dose exhibited no toxicity and significantly enhanced both humoral and cell-mediated immune responses, leading to higher antibody titres, increased T cell activation, and complete protection against a virulent NDV challenge. These findings suggest that the triple-TLR agonists' combination could improve vaccine efficacy and provide a cost-effective approach for vaccine formulations.

Peanut allergy is a significant worldwide health issue and requires innovative approaches to provide safer and more effective treatments. This study explores the potential of intradermal immunotherapy using peanut formulations combined with adjuvants. Six groups of BALB/c mice previously sensitized to peanut received intradermal treatments every other week for three months comprising of: Group 1 (G1) = Peanut extract (PE) + epinephrine (EPN); G2 = PE + EPN + topical Aldara® pretreatment; G3 = PE + EPN + topical imiquimod (IMQ) micellar gel pretreatment; G4 = PE + EPN + monophosphoryl lipid A (MPLA) + IMQ; G5 = PE + EPN + IMQ; G6 = Peanut powder + EPN + hyaluronic acid (HA). Clinical scores of peanut allergy, serological levels of peanut-specific IgE (Pe-IgE), IgG1, IgG2a, and histamine were compared before and after treatment, alongside studies on IMQ permeation and the pharmacokinetics of major peanut allergen ara h 2. Clinical scores improved significantly in all groups except G2 (trend towards improvement without statistical significance). Pe-IgE level decreased in G1, G2, and G3, while Pe-IgG1 increased in G1, G3, and G4. G3 alone showed a significant rise in Pe-IgG2a. No group was statistically superior to G1 after adjusting for differences in cumulative allergen doses received and initial IgE levels. Ex vivo experiments revealed that IMQ micellar gel in G3 enhanced skin permeation compared to Aldara®. Additionally, ara h 2 absorption was significantly reduced in naive mice treated with PE and HA. Baseline treatment of PE and EPN effectively reduced markers of peanut allergy. However, addition of TLR-agonist adjuvants or HA did not yield statistically significant improvements compared to baseline (G1).