Development and evaluation of recombinant Varicella-Zoster virus glycoprotein E protein microneedles for enhanced pediatric vaccine delivery

Abstract

Varicella-zoster virus (VZV) infection remains a significant pediatric health concern, and current live-attenuated vaccines are limited by cold-chain requirements, reactivation risk, and injection-related anxiety. To address these challenges, we developed and evaluated two recombinant VZV glycoprotein E (gE) microneedle (MN) platforms-coated microneedles (gE C-MN) and powder-attached microneedles (gE P-MN)-for painless, skin-targeted pediatric vaccination. Immunogenicity assessments in boosted BALB/c mice revealed comparable IgG antibody titers (> 15 log(2)) induced by gE P-MN, gE C-MN, and traditional intramuscular injection, indicating equivalent efficacy among delivery methods. Both MN formulation maintained antigen integrity during fabrication and exhibited excellent long-term stability at 25 degrees C over 12 months, with gE P-MN showing slightly superior stability compared to gE C-MN. Notably, both MN types significantly outperformed a liquid vaccine formulation in stability. Ex vivo porcine skin studies confirmed high intradermal delivery efficiency (> 95%) for both microneedle types. Additionally, both platforms demonstrated no skin irritation or pyrogenic effects in rabbit safety models. These findings demonstrate that powder-attached and coated microneedles effectively deliver recombinant VZV gE vaccines, satisfying essential requirements for pediatric immunization, including immunogenicity, storage stability, and safety. Thus, recombinant VZV gE microneedles represent a promising, user-friendly vaccine platform capable of enhancing compliance and vaccine accessibility, particularly in resource-limited regions..