Design, Synthesis, and Evaluation of Novel 1,2,3-Triazole-Tethered Glycolipids as Vaccine Adjuvants

Archiv der Pharmazie
Debabrata BhuniaM Sampath Kumar Halmuthur

Abstract

A Cu-mediated azide-alkyne click chemistry protocol was employed for the synthesis of a focused library of novel 1,2,3-triazolyl conjugates bearing various carbohydrate-steroid/triterpenoid entities. The immunogenicity of these compounds was examined initially by ex vivo assays. The lead compound 15g was further subjected to in vivo evaluation in BALB/c mice immunized with ovalbumin. These in vivo biological studies revealed an increase in B cell-mediated proliferation, higher expression levels of IL-2, TNF-α, IL-12, and IFN-γ indicating Th1 activation, together with an enhanced OVA-specific antibody (IgG) response compared to alum, affirming adjuvanticity of these glycolipids. The primary indications of response skewed toward Th1 immunity induced by the new triazoyl analogs indicate the potential of these molecules for possible application as adjuvants.

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Citations

Nov 10, 2020·Frontiers in Immunology·Simon ParisKarelle De Luca

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