Background
The COVID-19 pandemic laid bare global vulnerabilities in vaccine distribution, particularly the reliance on cold chain logistics and the need for clinician-administered injections. While nucleic acid-based vaccines like mRNA offer rapid adaptability, DNA vaccines present a more thermostable and cost-effective alternative. However, DNA vaccine deployment remains constrained by formulation and delivery challenges.
About the Project
This project, funded and facilitated by the Royce Industrial Collaboration Programme, and undertaken by the University of Nottingham and pharmaceutical company Avaxzipen Limited, addresses those barriers by using continuous extrusion manufacturing to create solid-dose DNA vaccine rods, representing a novel approach in the field. Unlike existing methods (e.g., moulding or tablet pressing), extrusion allows for more scalable production of mechanically robust doses.
Project Details and Results
This project developed SolidVAX – a high-payload, solid dosage form of a DNA vaccine by leveraging continuous extrusion, an innovative adaptation of existing materials processing techniques. Polymer formulations were optimised through systematic screening of excipients (e.g. PVP, MIRA-GEL®, methylcellulose, and other binders), and DNA stability was preserved using a freeze-drying step prior to extrusion. A bespoke extruder was designed and built to manufacture the solid vaccine rods. The final formulation allowed for consistent vaccine rod formation and high DNA loading (up to 100µg), confirmed by dsDNA assays and gel electrophoresis.
The vaccine rods were fabricated in two sizes to meet in vivo dosing requirements, with surface morphology validated by SEM imaging. Tartrazine dye and confocal microscopy confirmed even distribution, and rods dissolved completely within two minutes, meeting burst-release criteria.
Mechanical testing and dissolution studies confirmed rapid and robust release profiles, and in vivo testing showed good tolerance and compatibility. These findings represent a step change over current nucleic acid vaccine delivery strategies. They also demonstrate how advanced materials engineering can directly address critical bottlenecks in global vaccine deployment.
The successful demonstration of a thermostable, high-dose DNA vaccine platform supports broader efforts in pandemic preparedness, especially in resource-limited or remote regions. By eliminating cold chain requirements and enabling needle-free self-administration, this technology has the potential to enhance global vaccine equity, reduce healthcare costs, increase uptake among needle-phobic populations, and enable a more rapid response to emerging zoonotic threats.
Collaborators
SolidVAX pioneered the use of continuous extrusion manufacturing to produce high-payload, thermostable DNA vaccine solid-dose forms. Supported through Royce ICP funding, the project has demonstrated the ability to encapsulate up to 100µg of DNA into solid rods while maintaining structural integrity and bioactivity. This approach overcomes critical bottlenecks in global vaccine distribution, particularly cold chain dependency, and lays the foundation for future needle-free delivery systems. The work provides a new model for advanced materials innovation in the pharmaceutical sector, with potential applications beyond vaccination.
"This work represents an advance in vaccine delivery technology by pioneering a scalable, thermostable, and high-dose solid DNA vaccine platform using continuous extrusion manufacturing. By overcoming critical formulation and delivery challenges, it has the potential to transform global vaccination strategies, enabling needle-free, cold chain independent administration that can greatly improve vaccine access, equity, and rapid pandemic response, particularly in resource-limited settings."
Dr Robert Owen, Research Fellow, School of Pharmacy
University of Nottingham Biodiscovery Institute
