Date: 30th September 2019
A synthetic vaccine has been created for Chikungunya, a mosquito-borne virus. In a major advance in vaccine technology, the vaccine can be stored without refrigeration.
The small pox vaccine was the first successful vaccine to be developed by Edward Jenner in 1796. He inoculated a 13 year-old-boy with vaccinia virus (cowpox), and demonstrated immunity to smallpox, two years later the small pox vaccine was developed.
Vaccines are a crucial tool in infectious disease control.
Today, vaccination programmes are crucial for the control of infectious diseases across the globe, and whilst many diseases have been almost eradicated we have seen the devastating results when those such as Ebola or Zika have remained unchallenged.
The most devastating epidemics are usually seen in less developed areas of the world, where the infrastructure to deal and contain the pathogen is not available. Furthermore, climate and environmental changes are also allowing infectious diseases and their hosts to spread further and quicker than ever before.
Scientists from the UK and France have employed a self-assembling protein-based nanoparticle to create a vaccine for Chikungunya, a RNA virus, for which currently there is no specific antiviral drug treatment or commercially available vaccine.
In this case the nanoparticles in question were virus-like particles (VLPs). Closely resembling viruses, but devoid of viral genetic material they are non-infectious.
The VLPs are comprised of many copies of identical building blocks which resulted in highly repetitive surfaces. By coupling pathogen-derived epitopes to the structural units from which the VLPs self-construct, the epitopes reach a very high density, allowing them to elicit an immunogenic response.
In essence, the scientists have designed an antigen-presenting VLP platform, called ADDomer (adenovirus-derived multimeric protein-based self-assembling nanoparticle scaffold) to be a highly flexible, plug-and-play system which can display multiple immunogenic epitopes from a wide variety pathogens.
As a proof-of-concept, a Chikungunya vaccine was created, their design was validated by cryo-electron microscopy (cryo-EM), an electron microscopy technique applied to cryogenic samples.
Vaccine digital modelling
In collaboration with Oracle, a computer software company, the team was able to use Oracle’s high-performance cloud infrastructure to develop a novel computational approach to analyse the large dataset resulting from the cryo-EM.
As a result they created an accurate digital model of their synthetic vaccine, providing them with a novel, fast, and cost-effective mechanism to analyse the data. The resolution of the vaccine architecture was near-atomic, demonstrating the power of the system. In turn, this generated a rapid re-design process to model optimal variants of the vaccine.
The synthetic Chikungunya vaccine showed promising results when injected into mice, eliciting a very strong specific immunoglobulin G (IgG) response, demonstrating a robust place for this technology in the development of vaccines.
Thermo-stable advantage
By chance, the scientist discovered that the ADDomer particle was incredibly stable. When challenged with repeated rounds of freeze, thawing, storing at room temperature for weeks and heating to 45oC, the integrity of the Addomer remained intact.
This thermo tolerance will offer any Addomer vaccine a huge advantage both from a commercial perspective but also from a patient one. The ease of which it can be stored, shipped, and potentially stock piled will increase accessibility and will be a key to its future success. The system has been designed such that is can be used to create many other vaccines although it should be noted that the testing process is still very much in its infancy.
Nano-delivery system
One exciting area not yet explored is the potential the Addomer has as a delivery system. We have reported several cases in the recent months including synthetic nanocapsules delivering CRISPR for genome editing, and nanorobots targeting cancer cells.
With a cavity lying at the centre of the ADDomer nanoparticle, this can in theory be used to encase a cargo. The anticipation is that this new synthetic biology tool will have far reaching applications in a wide range of research and may find its way into the clinical tool box in the not so distant future. It is certainly one we will be keeping an interest in.
For more information please read the press release
Vragniau, C., J. C. Bufton, F. Garzoni, E. Stermann, F. Rabi, C. Terrat, M. Guidetti, V. Josserand, M. Williams, C. J. Woods, G. Viedma, P. Bates, B. Verrier, L. Chaperot, C. Schaffitzel, I. Berger and P. Fender (2019). “Synthetic self-assembling ADDomer platform for highly efficient vaccination by genetically encoded multiepitope display.” Science Advances 5(9): eaaw2853.
https://doi.org/10.1126/sciadv.aaw2853
