A TLR7 Agonist Conjugated to a Nanofibrous Peptide Hydrogel as a Potent Vaccine Adjuvant.

Autor: Euliano EM, Pogostin BH, Agrawal A, Yu MH, Baryakova TH, Graf TP, Hartgerink JD, McHugh KJ
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 09. Date of Electronic Publication: 2024 Mar 09.
DOI: 10.1101/2024.03.07.583938
Abstrakt: Toll-like receptors (TLRs) recognize pathogen- and damage-associated molecular patterns and, in turn, trigger the release of cytokines and other immunostimulatory molecules. As a result, TLR agonists are increasingly being investigated as vaccine adjuvants, though many of these agonists are small molecules that quickly diffuse away from the vaccination site, limiting their co-localization with antigens and, thus, their effect. Here, the small-molecule TLR7 agonist 1V209 is conjugated to a positively-charged multidomain peptide (MDP) hydrogel, K 2 , which was previously shown to act as an adjuvant promoting humoral immunity. Mixing the 1V209-conjugated K 2 50:50 with the unfunctionalized K 2 produces hydrogels that retain the shear-thinning and self-healing physical properties of the original MDP, while improving the solubility of 1V209 more than 200-fold compared to the unconjugated molecule. When co-delivered with ovalbumin as a model antigen, 1V209-functionalized K 2 produces antigen-specific IgG titers that were statistically similar to alum, the gold standard adjuvant, and a significantly lower ratio of Th2-associated IgG1 to Th1-associated IgG2a than alum, suggesting a more balanced Th1 and Th2 response. Together, these results suggest that K 2 MDP hydrogels functionalized with 1V209 are a promising adjuvant for vaccines against infectious diseases, especially those benefiting from a combined Th1 and Th2 immune response.
Table of Contents: Activation of toll-like receptors (TLRs) stimulates a signaling cascade to induce an immune response. A TLR7 agonist was conjugated to an injectable peptide hydrogel, which was then used to deliver a model vaccine antigen. This platform produced antibody titers similar to the gold standard adjuvant alum and demonstrated an improved balance between Th1- and Th2-mediated immunity over alum.
Databáze: MEDLINE
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