To improve malaria control, novel approaches are needed to enhance the efficacy of current vaccines and drug treatment approaches. Emerging evidence suggests that natural, drug-mediated, or vaccine-induced immunity against malaria is impeded by malaria-induced immunoregulatory pathways, which drive regulatory responses in both innate and adaptive cells. These immunoregulatory pathways are driven by Type I interferons (IFNs). As such, Type I IFNs are promising targets for improving anti-parasitic immunity, including in the context of malaria control programs. We identified an orally available, registered drug – ruxolitinib (Jakavi®) – that can suppress Type I IFN and enhance T cell immunity when combined with anti-parasitic drugs in animal models. We are currently testing whether ruxolitinib as an adjunctive, host directed therapy in combination with the anti-malarial drug artemether-lumefantrine (AL; Riamet®), can improve immune responses in malaria-naïve humans undergoing volunteer infection with P. falciparum induced blood-stage malaria. Redirecting the host immune response in infection has the potential to be an effective adjunct to boost protective immune development in response to malaria drug treatment, or malaria vaccination.