Adjuvants are added to vaccines to enhance the immune response and provide increased protection against disease. In the last decade, hundreds of synthetic immune adjuvants have been created, but many induce undesirable levels of proinflammatory cytokines including TNF-α and IL-6. Here we present small molecule NF-κB inhibitors that can be used in combination with an immune adjuvant to both decrease markers associated with poor tolerability and improve the protective response of vaccination. Additionally, we synthesize a library of honokiol derivatives identifying several promising candidates for use in vaccine formulations.
<p>Adjuvants
are added to vaccines to enhance the immune response and provide increased
protection against disease. In the last decade, hundreds of synthetic immune
adjuvants have been created, but many induce undesirable levels of
proinflammatory cytokines including TNF-a
and IL-6. Here we present small molecule NF-kB
inhibitors that can be used in combination with an immune adjuvant to both decrease
markers associated with poor tolerability and improve the protective response
of vaccination. Additionally, we synthesize a library of honokiol derivatives identifying
several promising candidates for use in vaccine formulations. <b></b></p>
Emerging diseases require generating new vaccines, which can often be time consuming. An alternate method to boost host defense is by inducing nonspecific innate immune memory, called trained immunity, to develop novel prophylactics. Many molecules, most notably β‐glucan, induce trained immunity, but their effects are often short‐lived and uncontrolled. This lack of temporal control limits both the therapeutic ability of training and provides fundamental questions about its nature. To achieve temporal control of trained immunity, controlled release nanoparticles encapsulating only 3.5% of the standard dose of β‐glucan to attain sustained release over a month are engineered. Nanoparticle‐trained mice exhibit prolonged training effects and improve resistance to a B16F10 tumor challenge compared to mice that receive an equivalent amount of free β‐glucan. The duration of trained immunity is further fine tuned by synthesizing nanoparticles composed of different molecular weights to modulate the release kinetics. These results demonstrate that dosing and temporal control can substantially alter the trained response to unanticipated levels. As such, this approach using sustained release platforms might lead to a novel prophylactic strategy for improved disease resistance against a wide variety of diseases.
<p>Adjuvants
are added to vaccines to enhance the immune response and provide increased
protection against disease. In the last decade, hundreds of synthetic immune
adjuvants have been created, but many induce undesirable levels of
proinflammatory cytokines including TNF-a
and IL-6. Here we present small molecule NF-kB
inhibitors that can be used in combination with an immune adjuvant to both decrease
markers associated with poor tolerability and improve the protective response
of vaccination. Additionally, we synthesize a library of honokiol derivatives identifying
several promising candidates for use in vaccine formulations. <b></b></p>
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