Exploiting Unique Features of Microneedles to Modulate Immunity

Abstract Microneedle arrays (MNAs) are small patches containing hundreds of short projections that deliver signals directly to dermal layers without causing pain. These technologies are of special interest for immunotherapy and vaccine delivery because they directly target immune cells concentrated in the skin. The targeting abilities of MNAs result in efficient immune responses—often more protective or therapeutic—compared to conventional needle delivery. MNAs also offer logistical benefits, such as self‐administration and transportation without refrigeration. Thus, numerous preclinical and clinical studies are exploring these technologies. Here the unique advantages of MNA, as well as critical challenges—such as manufacturing and sterility issues—the field faces to enable widespread deployment are discussed. How MNA design parameters can be exploited for controlled release of vaccines and immunotherapies, and the application to preclinical models of infection, cancer, autoimmunity, and allergies are explained. Specific strategies are also discussed to reduce off‐target effects compared to conventional vaccine delivery routes, and novel chemical and manufacturing controls that enable cargo stability in MNAs across flexible intervals and temperatures. Clinical research using MNAs is then examined. Drawbacks of MNAs and the implications, and emerging opportunities to exploit MNAs for immune engineering and clinical use are concluded.