The challenge
Viruses and virus-like particles are effective structural platforms for vaccine development and tools for intracellular delivery of therapeutic genes. The wide availability of these virus-derived products depends on:
- The reproducibility of their key quality attributes, including uniformity of shape and size
- Reliable and scalable manufacturing processes
Accurate measurements of viral particles remain challenging as they are small and complex structures. Even medium-size viruses, which constitute a popular choice for vaccines and gene therapy applications are <100 nm in diameter. The ability to characterise viruses and virus-like particles with nanoscale resolution is critical to increasing consistency and confidence. Accelerating innovation and manufacturing has a significant impact on costs, timescale and accessibility to vaccines and gene therapies.
The solution
High resolution microscopy measurements performed using transmission electron microscopy (TEM) provide a solution to this challenge. In a recently completed A4I project, NPL applied its expertise in molecular biophysics and nanoscale imaging to characterise novel viral vaccines. These were developed to prevent several diseases, such as those caused by the Zika virus, by Activirosomes Limited in an SBRI funded project with their inventor, Seagull Biosolutions Pvt Ltd.
NPL scientists used a range of biophysical measurements, combined with transmission electron microscopy, to obtain crucial information on the size and stability of the vaccines and batch-to-batch variations, which are common for virus-based products. Additionally, information on their intracellular distribution obtained by TEM was used to support bioactivity data.
It was an exciting collaboration. Not only we were able to visualise the viruses with nanoscale precision, quantitatively and in their native environment, but it also proved possible to establish direct correlations with bioactivity data
Emiliana De Santis, Senior Research Scientist - NPL
The impact
Visualisation of virus-derived products is a critical step during their production, quality control and testing. Reliable information on their physical characteristics can shorten development time and inform more cost-effective manufacturing approaches that can be used to make rapid and specific changes to manufacturing processes and materials.
Visualisation of viral structures provided critical information to support the development of these novel viral vaccine platforms and the optimisation of their manufacturing processes.
The study gave reliable information on the physical characteristics of the viral vaccines, batch to batch variation and supported to the biological activity data, which is expected to contribute to shorter development time.
In addition, it will inform more cost-effective manufacturing approaches that can be used to make rapid and specific changes to processes and materials.