Toll-like receptor (TLR) agonists as a driving force behind next-generation vaccine adjuvants and cancer therapeutics |
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Affiliation: | 1. Department of Chemistry and Centre for Advanced Studies, Panjab University, Chandigarh, India;2. National Interdisciplinary Centre of Vaccines, Immunotherapeutics and Antimicrobials, Panjab University, Chandigarh, India;3. Vaxine Pty Ltd., Bedford Park, Adelaide 5042, Australia;4. College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia |
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Abstract: | Until recently, the development of new human adjuvants was held back by a poor understanding of their mechanisms of action. The field was revolutionized by the discovery of the toll-like receptors (TLRs), innate immune receptors that directly or indirectly are responsible for detecting pathogen-associated molecular patterns (PAMPs) and respond to them by activating innate and adaptive immune pathways. Hundreds of ligands targeting various TLRs have since been identified and characterized as vaccine adjuvants. This work has important implications not only for the development of vaccines against infectious diseases but also for immuno-therapies against cancer, allergy, Alzheimer's disease, drug addiction and other diseases. Each TLR has its own specific tissue localization and downstream gene signalling pathways, providing researchers the opportunity to precisely tailor adjuvants with specific immune effects. TLR agonists can be combined with other TLR or alternative adjuvants to create combination adjuvants with synergistic or modulatory effects. This review provides an introduction to the various classes of TLR adjuvants and their respective signalling pathways. It provides an overview of recent advancements in the TLR field in the past 2–3 years and discusses criteria for selecting specific TLR adjuvants based on considerations, such as disease mechanisms and correlates of protection, TLR immune biasing capabilities, route of administration, antigen compatibility, new vaccine technology platforms, and age- and species-specific effects. |
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Keywords: | Toll-like receptor Adjuvant TLR signalling Vaccine Immune bias PAMP" },{" #name" :" keyword" ," $" :{" id" :" pc_atbo1icTOJ" }," $$" :[{" #name" :" text" ," _" :" pathogen-associated molecular pattern TLR" },{" #name" :" keyword" ," $" :{" id" :" pc_y12h81AraN" }," $$" :[{" #name" :" text" ," _" :" toll-like receptor MYD88" },{" #name" :" keyword" ," $" :{" id" :" pc_hQjxzh5lpK" }," $$" :[{" #name" :" text" ," _" :" Myeloid differentiation primary response-88 TRAM" },{" #name" :" keyword" ," $" :{" id" :" pc_PFyZCwHHni" }," $$" :[{" #name" :" text" ," _" :" TRIF-related adaptor molecule MAL" },{" #name" :" keyword" ," $" :{" id" :" pc_5ZoOpQ5lVS" }," $$" :[{" #name" :" text" ," _" :" MyD88 adaptor-like TIRAP" },{" #name" :" keyword" ," $" :{" id" :" pc_Ecybaywcpj" }," $$" :[{" #name" :" text" ," _" :" TIR domain-containing adaptor protein APC" },{" #name" :" keyword" ," $" :{" id" :" pc_SfxmfQXPvq" }," $$" :[{" #name" :" text" ," _" :" antigen presenting cells pDC" },{" #name" :" keyword" ," $" :{" id" :" pc_3zEQcVbWd8" }," $$" :[{" #name" :" text" ," _" :" Plasmacytoid dendritic cells BCR" },{" #name" :" keyword" ," $" :{" id" :" pc_xfKrtbKn1g" }," $$" :[{" #name" :" text" ," _" :" B cell receptors BLIMP-1" },{" #name" :" keyword" ," $" :{" id" :" pc_XiGhWhdV4H" }," $$" :[{" #name" :" text" ," _" :" B lymphocyte-induced maturation protein-1 LLPCs" },{" #name" :" keyword" ," $" :{" id" :" pc_ylLGgKJZ6o" }," $$" :[{" #name" :" text" ," _" :" long-lived plasma cells IRAK" },{" #name" :" keyword" ," $" :{" id" :" pc_HEFjDsvPTn" }," $$" :[{" #name" :" text" ," _" :" IL1-receptor associated kinase TRAF" },{" #name" :" keyword" ," $" :{" id" :" pc_kGw72vhXlX" }," $$" :[{" #name" :" text" ," _" :" TNF receptor-associated factor MAPK" },{" #name" :" keyword" ," $" :{" id" :" pc_4cpBtj8ntZ" }," $$" :[{" #name" :" text" ," _" :" mitogen-activated protein kinase NF-κB" },{" #name" :" keyword" ," $" :{" id" :" pc_GhUT1n6pBC" }," $$" :[{" #name" :" text" ," _" :" nuclear factor kappa B IRF" },{" #name" :" keyword" ," $" :{" id" :" pc_pqoz1GGAKt" }," $$" :[{" #name" :" text" ," _" :" interferon-regulatory factor RIP" },{" #name" :" keyword" ," $" :{" id" :" pc_8Bpc5LFmn0" }," $$" :[{" #name" :" text" ," _" :" receptor interacting protein CTL" },{" #name" :" keyword" ," $" :{" id" :" pc_Nja7QwnqPC" }," $$" :[{" #name" :" text" ," _" :" cytotoxic T-cell ERK" },{" #name" :" keyword" ," $" :{" id" :" pc_tF7VDi4JEQ" }," $$" :[{" #name" :" text" ," _" :" extracellular signal-regulated kinases PI3K" },{" #name" :" keyword" ," $" :{" id" :" pc_ZiizprQL57" }," $$" :[{" #name" :" text" ," _" :" phosphoinositide 3-kinase NOD" },{" #name" :" keyword" ," $" :{" id" :" pc_MK3Z89uvJY" }," $$" :[{" #name" :" text" ," _" :" nnucleotide oligomerization domain LPS" },{" #name" :" keyword" ," $" :{" id" :" pc_a2BxkFrhaX" }," $$" :[{" #name" :" text" ," _" :" lipopolysaccharides ssRNAs" },{" #name" :" keyword" ," $" :{" id" :" pc_V7nD6sTNRz" }," $$" :[{" #name" :" text" ," _" :" stranded ribonucleic acids ORNs" },{" #name" :" keyword" ," $" :{" id" :" pc_VmgRvTjAN1" }," $$" :[{" #name" :" text" ," _" :" oligoribonucleotides OVA" },{" #name" :" keyword" ," $" :{" id" :" pc_SFHCCZJrO4" }," $$" :[{" #name" :" text" ," _" :" ovalbumin |
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