Design, Synthesis, and Evaluation of Novel 1,2,3-Triazole-Tethered Glycolipids as Vaccine Adjuvants.
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.
Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Debabrata
D
Bhunia
Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Preethi M C
PM
Pallavi
Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Srinivasa Reddy
SR
Bonam
Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Sandeep A
SA
Reddy
Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Yogesh
Y
Verma
Vaccine Immunology Laboratory, Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
M Sampath Kumar
MS
Halmuthur
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015195:Drug Design; D006017:Glycolipids / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D006461:Hemolysis / Q000187:drug effects; D007114:Immunization; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology*; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D006017:Glycolipids; D007074:Immunoglobulin G; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C041524:aluminum sulfate; D007371:Interferon-gamma; D010047:Ovalbumin
1,2,3-Triazoles; Adjuvant; Click chemistry; Glycolipids; Th1 immunity