Innate Immune Memory for Improved Vaccine Response

Abstract

Abstract 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 improve on the capabilities of β-glucan, we developed a method for temporal control of trained immunity and examined its use both as a prophylactic and as an additive for improve vaccine outcomes. We engineered controlled release nanoparticles encapsulating only 3.5% the standard dose of β-glucan to attain sustained release over a month. Nanoparticle trained mice exhibited prolonged training effects and improved resistance to a B16F10 tumor challenge compared to mice that received an equivalent amount of free β-glucan. We also showed that trained mice exhibited higher antibody responses upon vaccination. 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. HDTRA11810052