| News from the projects VSV-EBOVAC identifies signature of promising Ebola vaccine How exactly does our immune system respond to vaccination? In the first study of its kind, scientists from IMI’s VSV-EBOVAC project, studying a promising Ebola vaccine, set out to find out which immune cells get activated early on, which inflammatory markers are released after that, and how this early activity later impacts the production of antibodies against the Ebola virus. In the process, they discovered a unique signature of a promising Ebola vaccine candidate which could not only help predict adverse reactions and the effectiveness of this vaccine, but also inform the development of vaccines for other diseases as well. ‘These findings are important and indeed ground-breaking,’ said Claire-Anne Siegrist of the University of Geneva, the project's scientific coordinator. ‘No signature for this vaccine or any other Ebola vaccine has been previously identified. On a clinical level, this plasma signature can serve as a biological clue (biomarker) to anticipate and determine common side effects and the ability of our bodies to produce protective antibodies against the Ebola virus.’ The findings, which were published in the prestigious journal Science Translational Medicine, wouldn’t have been possible without IMI, she added. ‘The public-private nature of the project was tremendously important in achieving these results. In addition to academic partners, representatives of the vaccine manufacturers played a very important role in the study.’ ‘This was a highly valuable experience for us’ – meet the SME in IMI’s EBOMAN project Vibalogics, a small-to-medium sized enterprise (SME) from Germany, is the managing entity of IMI’s EBOMAN project. Although the company had no prior experience with IMI or Horizon 2020 (H2020) projects, they prepared their submission for EBOMAN in only four weeks and won the grant. Two years later, they achieved a big milestone: the building of a new, state-of-the art filling line to speed up the production of live vaccines for clinical trials.The IMI programme office interviewed Stefan Beyer, managing director of Vibalogics, about his company's experiences of setting up and running an IMI project. ‘This was a highly valuable experience for us’, he said . ‘Firstly, we have been very proud to have been selected for this grant – this honours all the work we have done in the past to establish our company in this niche. Participating in IMI triggered and accelerated the expansion of our business and it brought us more customers. It also helped us to establish new partnerships and increased our visibility on a global level. All taken together, it has been very beneficial for us.’ RAPP-ID test could speed up flu diagnosis Flu is a highly infectious disease, yet during an epidemic, it can be hard to identify which patients have the virus. A device under development by IMI’s RAPP-ID project could deliver a flu diagnosis faster and without the hassle of an invasive nasal swab. Patients would simply have to breathe into a bottle-like container for a few minutes to get a near-instant result at the point of care, which could be their doctor’s surgery or even their own home. Inside the device, the first step involves using highly-charged needles to direct the micro-droplets of water in the exhaled breath that carry the virus to a droplet of liquid in the bottom of the chamber. There, the walls of the virus are broken down and the viral proteins bind to specially designed magnetic beads coated with antibodies. The beads are then flushed into an array of tens of thousands of minute wells, each smaller than a red blood cell. Finally, additional reagents are brought to the array, causing the flu proteins to glow so that they can be counted with a camera. The different components have been demonstrated to work independently, as described in three papers in PLoS ONE, Applied Materials and Interfaces, and Analytical Chemistry. Now the team is keen to continue its work on the device. Meanwhile, lead researcher Professor Wouter van der Wijgaart from the KTH Royal Institute of Technology in Sweden, explains: ‘This kind of test will enable doctors to treat severely threatened patients the right way, and it will be valuable for use in clinical research. It’s harder than finding a needle in a haystack, but it can be done.’ Newly-identified molecules could block action of protein behind rheumatoid arthritis Scientists have identified two molecules that block the action of a protein implicated in many inflammatory diseases such as rheumatoid arthritis. The findings, published in the journal PLoS Computational Biology, could lead to the development of much-needed new treatments for these diseases. The work was funded in part through IMI’s BTCure project. The protein tumour necrosis factor (TNF) has been implicated in a number of inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, psoriasis, and multiple sclerosis. Drugs blocking the activity of TNF have been developed as treatments for these diseases; however, they do not work in all patients, they can cause unpleasant side effects, and their effectiveness can wear off over time. In this study, scientists used a computer tool to virtually screen 15 000 small molecules in a quest to identify those that could interfere with the activity of TNF and RANKL, a protein that is a member of the TNF family. This virtual search identified nine promising molecules, which the team subjected to detailed studies in in the laboratory. These ‘real life’ studies showed that two of the molecules, T23 and T8, showed particularly strong activity as inhibitors of TNF and RANKL, preventing them from interacting properly with other proteins. ‘These compounds present low toxicity and may be further optimised in drug design targeting TNF and RANKL to develop improved treatments for a range of inflammatory and autoimmune diseases,’ the researchers conclude. CANCER-ID finds clues to cancer drug effectiveness in blood Changes in the genes of cancer cells found in the blood could help to identify patients for whom a standard drug is most likely to be effective, according to a new study by scientists from IMI’s CANCER-ID project. The findings, published in the journal Cancer Research, could ultimately result in tests that would allow doctors to distinguish between patients who should keep taking the drug and patients who would benefit from trying alternative treatments. The scientists focused on a form of non-small cell lung cancer (NSCLC) that is driven by mutations in a gene called ALK. There is a drug, crizotinib, that targets ALK. However, while crizotinib helps some patients to keep the cancer in check for years, in others its effects last for just a few months. The challenge for doctors is to identify which patients are unlikely to respond well to treatment, so that they can be offered a different treatment. It is not practical to subject NSCLC patients to regular biopsies to track the progress of their disease. However, some cancer cells break off from the tumour and enter the blood stream. These circulating tumour cells (CTCs) can be identified and analysed via a simple blood test. In this latest study, scientists took blood samples from ALK-NSCLC patients both before and two months after starting crizotinib treatment. They then analysed the CTCs found in the blood samples for both ALK rearrangements and multiple copies of the ALK gene. This revealed that patients who showed a decrease in the number of CTCs with multiple copies of the ALK gene after two months on crizotinib had an average progression free survival (i.e. their condition did not worsen) of 14 months. In comparison, patients where the number of CTCs with multiple copies of the ALK gene stayed the same or increased had an average progression free survival of just six months. ‘In this study, we showed that analysis of ALK copy number in CTCs before starting crizotinib treatment and after two months of crizotinib treatment may provide a biomarker for predicting the effectiveness of the therapeutic,’ said the lead author of the paper, Françoise Farace of INSERM in France. ‘This is important because there is currently no means of distinguishing those patients likely to gain long-term benefit from crizotinib from those who are not and who should consider trying some of the newer ALK-targeted therapeutics that have been more recently developed.’ Larger studies are now needed to validate the findings, and the technology used to study the CTCs is not yet ready for large-scale application. Nevertheless, Dr Farace points out: ‘The results reflect the potential of liquid biopsies to monitor treatment response in real time and tailor treatments at the individual patient level.’ |
