Buccal microneedle-delivered ferritin nanovaccines induce strong respiratory immunity against Pseudomonas aeruginosa

Abstract

Mucosal vaccines provide a crucial first-line defense against invading pathogens by inducing secretory IgA (sIgA) at mucosal surfaces. While subunit antigen based mucosal vaccines offer improved safety profiles, their development faces two tremendous challenges: inherently poor mucosal immunogenicity and inefficient antigen delivery across mucosal barriers. Here, we demonstrate ferritin nanovaccine incorporated dissolving microneedles are effective against Pseudomonas aeruginosa (PA) infection via buccal mucosal immunization. The nanovaccine was engineered through conjugating the PA antigen PcrV_NH to ferritin nanoparticles using SpyTag/SpyCatcher system. This microneedles vaccine demonstrated efficient mucosal penetration and recruitment of antigen-presenting cells at the penetration sites. Notably, the used ferritin nanoparticles showed potent mucosal adjuvanticity as indicated by the improved antigen uptake, activation of the antigen-presenting cells and the amplification of the both mucosal and systemic humoral and cellular immune responses. Finally, it induced potent sIgA production in respiratory mucosal secretions and systemic immune responses, providing effective protection against PA pulmonary infection. Our findings establish ferritin nanovaccines combined with microneedles delivery as a promising strategy for developing safe and effective mucosal subunit vaccines.