Microneedle-based Rabies Vaccination: A Promising Approach Toward the WHO “Zero by 30” Target

Hosseini Tehrani, Mehrnaz; Aramideh Khouy, Reza; Malek-Khatabi, Atefeh; Rad-Malekshahi, Mazda; Kachooei, Atefeh; Shahali, Maryam; Peirovi, Babak; Mousavizadeh, Leila; Keyvani, Hossein; Ataei‐Pirkooh, Angila

doi:10.32598/ARI.81.1.3942

Microneedle-based Rabies Vaccination: A Promising Approach Toward the WHO “Zero by 30” Target

Document Type : Original Articles

Authors

¹ Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

² Center for Advanced Biomaterials for Health Care (CABHC), Italian Institute of Technology, Napoli, Italy.

³ Department of Pharmaceutical Biomaterials, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

⁴ Department of Viral Vaccines Production, Research and Production Complex, Pasteur Institute of Iran, Tehran, Iran.

⁵ Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

10.32598/ARI.81.1.3942

Abstract

Introduction: Rabies remains a fatal zoonotic disease causing tens of thousands of deaths annually, predominantly in resource-limited countries, where intramuscular (IM) vaccines are limited by cost, cold-chain needs, and the need for skilled administration. Achieving the World Health Organization’s “Zero by 30” target necessitates innovative, scalable, and cost-effective vaccine delivery approaches. In this study, we developed dissolving microneedle (MN) patches (dMNPs) loaded with rabies vaccine using hyaluronic acid (HA) and polyvinylpyrrolidone (PVP) as biocompatible and biodegradable polymers.
Materials & Methods: An aluminum master mold fabricated by CNC machining contained 400 cubical-pyramidal MNs (800 µm height, 300×300 µm base), while PDMS replicas enabled precise two-step centrifugal casting. Morphology, virion integrity, mechanical strength, and ex vivo skin penetration were evaluated. Bagg Albino/subline C (BALB/c) mice received two doses of vaccine-loaded microneedles, IM injection, or blank patches, and virus-neutralizing antibodies were measured.
Results: MNs exhibited uniform geometry (651.2±4.3 μm height), high mechanical strength (0.403±0.006 N/needle), and reliable skin penetration (~300 μm). Transmission electron microscopy confirmed that rabies virions retained their bullet-shaped morphology after encapsulation and storage. Rabies virus-neutralizing antibodies showed comparable titers four weeks post-booster: dMNP (1 mg; geometric mean titers (GMTs): 7.67 IU/mL, 95% CI, 6.8%, 8.64%) versus IM (10 mg; GMT: 6.95 IU/mL, 95% CI, 6.2%, 7.8%; P>0.05), both surpassing protective thresholds (≥0.5 IU/mL), while controls remained seronegative.
Conclusion: Beyond achieving robust immune responses, these dMNPs provide dose-sparing, thermostability, self-administration, and sharps-free delivery—which enhance feasibility, acceptance, and scalability, aligning with the WHO’s “Zero by 30” target. This platform offers translational potential for equitable rabies prophylaxis in resource-limited settings.

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