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

Abstract

Microneedle array (MNA) has proven more efficient in stimulating humoral immunity than intramuscular (IM) vaccination. However, its effectiveness in inducing pulmonary CD8+ T cells remains elusive, which is essential to the frontline defense against pulmonary viral infections like influenza and covid19 viruses. The current investigation reveals that superior CD8+ T cell responses are elicited by MNA immunization over intradermal (ID) or IM immunization using the model antigen ovalbumin (OVA), irrespective of whether or not the antigen is provided in the lung. Mechanistically, MNA immunization targeted the epidermal layer and stimulated predominantly Langerhans cells resulting in increased expression of α4β1 adhesion molecule on CD8+ T cell surface, which may play a role in T-cell homing to the lung, whereas CD8+ T cells induced by IM immunization did not express the adhesion molecule sufficiently. CD8+ T cells with a lung-homing propensity were also seen after ID vaccination, yet to a much lesser extent.Accordingly, MNA immunization provided stronger protection against influenza viral infection than an ID or IM 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.