Breakthrough in Synthetic Vaccine Technology Requires No Refrigeration, Hacker News

Infectious diseases continue to plague populations worldwide. Among the means at our disposal to counter this threat, vaccination has proven to be exceptionally powerful. Smallpox has been eradicated, measles, polio and tetanus constrained from the world by vaccination. However, severe challenges to human health persist, evidenced by epidemics caused by Ebola, Zika and others. This is particularly severe in developing countries which often lack adequate infrastructure and resources to prevent or manage outbreaks, bringing about disruption and damage in affected communities and massive economic shortfall.

A recent example is Chikungunya, a virus transmitted by the bite of an infected mosquito. The disease causes crippling headache, vomiting, swelling of limbs and can lead to death. Even if a fever ends abruptly, chronic symptoms such as intense joint pain, insomnia and extreme prostration remain. Formerly confined to sub-Saharan Africa, Chikungunya has recently spread worldwide as its mosquito host leaves its natural habitat due to deforestation and climate change, with recent outbreaks in USA and Europe causing alarm.

Researchers from the University of Bristol and theFrench National Center for Scientific Research(CNRS) in Grenoble, France, teamed up with computer technology giantOracleto find a way to make vaccines that are thermostable (able to withstand warm temperatures), can be designed quickly and are easily produced.

“We were working with a protein that forms a multimeric particle resembling a virus but is completely safe, because it has no genetic material inside, said Pascal Fender, expert virologist at CNRS.” Completely by chance, we discovered that this particle was incredibly stable even after months, without refrigeration. “

“This particle has a very flexible, exposed surface that can be easily engineered, addedImre Berger,Director of theMax Planck-Bristol Center for Minimal Biologyin Bristol. “We figured that we could insert small, harmless bits of Chikungunya to generate a virus-like mimic we could possibly use as a vaccine. “

To validate their design, the scientists employed cryo-electron microscopy, a powerful new technique recently installed in Bristol’s state-of-the-the-art microscopy facility headed byChristiane Schaffitzel, co-author of the study. Cryo-EM yields very large data sets from which the structure of a sample can be determined at near atomic resolution, requiring massive parallel computing.

Enabled by Oracle’s high-performance cloud infrastructure, the team developed a novel computational approach to create an accurate digital model of the synthetic vaccine. Specialists Rahaf MasriChristopher WoodsandMatt Williams,together with colleagues at Oracle, implemented software packages seamlessly on the cloud in this pioneering effort. Christopher explained: “We were able to process the large data sets obtained by the microscope on the cloud in a fraction of the time and at much lower cost than previously thought possible.”

“Researchers have had a long tradition of building and installing their own super computers on-premises, but cloud computing is allowing them to run large data sets in record time, with fast connectivity and low latency. helping them crunch data and make scientific breakthroughs much faster. Going forward, technologies like machine learning and cloud computing will play a significant part in the scientific world, and we are delighted we could help the researchers with this important discovery, “added Phil Bates, leading cloud architect at Oracle.

The particles the scientists designed yielded exceptionally promising results in animal studies, soundly setting the stage for a future vaccine to combat Chikungunya disease.

“We were thoroughly delighted,” continued Imre Berger. “Viruses are waiting to strike, and we need to have the tools ready to tackle this global threat. Our vaccine candidate is easy to manufacture, extremely stable and elicits a powerful immune response. It can be stored and transported without refrigeration to countries and patients where it is most needed. Intriguingly, we can now rapidly engineer similar vaccines to combat many other infectious diseases just as well. “

“It really ticks a lot of boxes,” concluded Fred Garzoni, founder of Imophoron Ltd, a Bristol biotech start-up developing new vaccines derived from the present work. “Many challenges in the industry require innovative solutions, to bring powerful new vaccines to patients. Matching cutting-edge synthetic biology with cloud computing turned out to be a winner.”

The authors would like to thank theFinovi Foundation, theAgence National de Recherche(ANR),the Elizabeth Blackwell Institute, theEPSRC,BBSRC,Wellcome TrustandGW4for their support.

Paper

‘Synthetic self-assembling ADDomer platform for highly efficient vaccination by genetically- encoded multi-epitope display‘by Vragniauet alinScience Advances

Further information

Imre Berger is also Co-Director of theBristol BioDesign Institutewhich focuses on biomolecular design and engineering in synthetic biology. He is co-founder ofImophoron Ltdand partner in the EPSRC Innovation Vaccine Manufacturing Hub.

Key facts:(source: World Health Organization)

• Chikungunya is a viral disease transmitted to humans by infected mosquitoes. It causes fever, severe joint pain, chronic arthritis, fatigue andad extremisdeath.
• Recent Chikungunya outbreaks caused greatly human suffering and economic shortfall in affected communities.
• The disease shares some clinical signs with dengue and zika which are spread by the same mosquito.
• There is no cure or preventive vaccine. Treatment is focused on relieving the symptoms.
• The disease mostly occurs in Africa, Asia and the Indian subcontinent. However, a major outbreak in 2015 affected several countries of the region of the Americas.
• Due to climate change and deforestation, mosquitos leave the natural sub-Saharan habitat spreading the disease world-wide.

About the Max Planck-Bristol Center for Minimal Biology
TheMax Planck-Bristol Center for Minimal Biology(MPBC), a partnership between the University of Bristol and the Max Planck Society for the Advancement of Science (MPG) in Germany, seeks to understand the foundations of life and how it arose from non-living matter by designing and building artificial cells, minimal genomes, virus-like nanodevices and new cellular scaffolds.

About the Bristol BioDesign Institute
TheBristol BioDesign Institute(BBI) co-ordinates synthetic biology research, training and innovation across the University of Bristol. With wide-ranging applications from health to food security, BBI exploits pioneering approaches to deliver the rational design and engineering of biological systems for useful purposes, through multidisciplinary research which brings together postgraduate and postdoctoral researchers, academics, policy makers and industry, whilst also engaging the public with emerging solutions to global challenges.

About the electron cryo-microscope facility at Bristol
(The) ********************** (GW4 alliance) ‘s state-of-the-art facility for high-resolution electron cryo-microscopy provides access to cryo-microscopy and analysis tools to researchers from diverse disciplines across the Great West region (Bath, Bristol, Cardiff, Exeter) and beyond. The facility enables near-atomic study of molecular architectures in cell function using single particle cryo-EM or cryo-tomography, providing unique insights in mechanisms in health and disease. The facility received funding from the Wellcome Trust, the BBSRC and the GW4 alliance partner institutions.

About Imophoron Ltd – innovative vaccine company
Bristol start-up Imophoron’s ambition is to bring about a revolution in the fight against deadly pathogens and to tackle current challenges met by the vaccine industrywith Imophoron’s next -generation vaccine development platform. Imophoron won theLaunch Great West Global Good Award.

About Oracle
The Oracle Cloud offers a complete suite of integrated applications for sales, service, marketing, human resources, finance, supply chain and manufacturing, plus highly automated and secure generation 2 infrastructure featuring the Oracle Autonomous Database. For more information about Oracle (NYSE: ORCL), visitwww.oracle.com

About the Elizabeth Blackwell Institute
(TheElizabeth Blackwell Institute for Health Researchis building a dynamic community of researchers from our health and non-health related disciplines to find innovative solutions for some of the most pressing health challenges of the 21 st century. The Institute will achieve this through encouraging new ways of working, and also through fostering collaborative approaches between scientists, industry, clinical practitioners and patients.