Microneedle-Mediated Immunization Promotes Lung CD8+ T-Cell Immunity

Microneedle array has proven more efficient in stimulating humoral immunity than intramuscular vaccination. However, its effectiveness in inducing pulmonary CD8+ T cells remains elusive, which is essential to the frontline defense against pulmonary viral infections such as influenza and COVID-19 viruses. The current investigation reveals that superior CD8+ T-cell responses are elicited by immunization with a microneedle array over intradermal or intramuscular immunization using the model antigen ovalbumin, irrespective of whether or not the antigen is provided in the lung. Mechanistically, microneedle array-mediated immunization targeted the epidermal layer and stimulated predominantly Langerhans cells, resulting in increased expression of α4β1 adhesion molecules on the CD8+ T-cell surface, which may play a role in T-cell homing to the lung, whereas CD8+ T cells induced by intramuscular immunization did not express the adhesion molecule sufficiently. CD8+ T cells with a lung-homing propensity were also seen after intradermal vaccination, yet to a much lesser extent. Accordingly, microneedle array immunization provided stronger protection against influenza viral infection than intradermal or intramuscular immunization. The observations offer insights into a strong cross-talk between epidermal immunization and lung immunity and are valuable for designing and delivering vaccines against respiratory viral infections.