Psychopharmacology · 2019
Psychopharmacology: neuroimmune signaling in psychiatric disease-developing vaccines against abused drugs using toll-like receptor agonists.
СтатьяОбзорНазвание и аннотация: Перевод в очереди
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Yang Fang, Kosten Thomas R
Аннотация
RATIONALE: Since substance use disorders have few or no effective pharmacotherapies, researchers have developed vaccines as immune-therapies against nicotine, cocaine, methamphetamine, and opioids including fentanyl.
OBJECTIVES: We focus on enhancing antibody (AB) production through stimulation of toll-like receptor-5 (TLR5) during active vaccination. The stimulating adjuvant is Entolimod, a novel protein derivative of flagellin. We review the molecular and cellular mechanisms underlying Entolimod's actions on TLR5.
RESULTS: Entolimod shows excellent efficacy for increasing AB levels to levels well beyond those produced by anti-addiction vaccines alone in animal models and humans. These ABs also significantly block the behavioral effects of the targeted drug of abuse. The TLR5 stimulation involves a wide range of immune cell types such as dendritic, antigen presenting, T and B cells. Entolimod binding to TLR5 initiates an intracellular signaling cascade that stimulates cytokine production of tumor necrosis factor and two interleukins (IL-6 and IL-12). While cytokine release can be catastrophic in cytokine storm, Entolimod produces a modulated release with few side effects even at doses 30 times greater than doses needed in these vaccine studies. Entolimod has markedly increased AB responses to all of our anti-addiction vaccines in rodent models, and in normal humans.
CONCLUSIONS: Entolimod and TLR5 stimulation has broad application to vaccines and potentially to other psychiatric disorders like depression, which has critical inflammatory contributions that Entolimod could reduce.
OBJECTIVES: We focus on enhancing antibody (AB) production through stimulation of toll-like receptor-5 (TLR5) during active vaccination. The stimulating adjuvant is Entolimod, a novel protein derivative of flagellin. We review the molecular and cellular mechanisms underlying Entolimod's actions on TLR5.
RESULTS: Entolimod shows excellent efficacy for increasing AB levels to levels well beyond those produced by anti-addiction vaccines alone in animal models and humans. These ABs also significantly block the behavioral effects of the targeted drug of abuse. The TLR5 stimulation involves a wide range of immune cell types such as dendritic, antigen presenting, T and B cells. Entolimod binding to TLR5 initiates an intracellular signaling cascade that stimulates cytokine production of tumor necrosis factor and two interleukins (IL-6 and IL-12). While cytokine release can be catastrophic in cytokine storm, Entolimod produces a modulated release with few side effects even at doses 30 times greater than doses needed in these vaccine studies. Entolimod has markedly increased AB responses to all of our anti-addiction vaccines in rodent models, and in normal humans.
CONCLUSIONS: Entolimod and TLR5 stimulation has broad application to vaccines and potentially to other psychiatric disorders like depression, which has critical inflammatory contributions that Entolimod could reduce.