86th Edition – January 2019

ULTRA-DD makes details of antibodies open access

The ULTRA-DD project has published details of an antibody against interleukin-8 that can be used in research on diseases such as rheumatoid arthritis. By making the sequence and other details public through open access, the team hopes that other researchers will be able to use them and adapt them for their own research.

In our bodies, our immune system produces antibodies to defend us from infectious diseases. It is also possible to produce antibodies in the lab. In some cases, these are used as treatments for disease. While the quality of these treatment-grade antibodies is very high, they are protected by intellectual property rules and so their use in research is limited. Many more antibodies are used in drug development, to study possible drug targets for example. However, the quality of these research-grade antibodies is often poor, and this makes results generated using them unreliable. One major problem in the world of antibodies is the reluctance of some researchers to publish the sequences of antibodies they develop.

Now, ULTRA-DD is working to change this situation. They are using the latest techniques to generate and validate new antibodies in collaboration with the clinical research community and external commercial partners and are publishing the results on the project website.

‘Our antibodies have their sequences revealed and they are open access, meaning that we want other researchers in companies and academia to pick them up and use them without restrictions,’ said the project’s Susanne Gräslund of Karolinska Insitutet. ‘As the sequences are known they can be easily converted to other formats and modified if needed.’

The first antibody released, against interleukin-8, will be primarily of interest to the rheumatoid arthritis field, but could also be relevant for researchers working on other inflammatory diseases and possibly also cancer. ‘We also hope that our project can serve as a good example for sharing sequences for antibodies and more openness in the field,’ concluded Dr Gräslund.

DRIVE publishes results of pilot study on flu vaccine effectiveness

The DRIVE project has published a report on its pilot study on flu vaccine effectiveness during the 2017-2018 season. The learnings from the pilot are now being implemented in a larger scale multi-centre study during this winter’s flu season.

Seasonal influenza affects millions of Europeans every year and can kill between 15 000 and 70 000 of them. Vaccination is recognised as the best way to protect the vulnerable from the disease. However, the flu virus is constantly changing, so every year vaccine manufacturers need to make new versions of the vaccine, based on advice from the World Health Organization on the virus strains most likely to be in circulation in the near future.

Vaccines vary in a number of ways; for example, most contain inactivated viruses and are injected, while some contain live but weakened viruses and are given as a nasal spray. Some include an adjuvant to boost the immune response, while others do not. Manufacturing methods also vary.

Until now, data on the effectiveness of different vaccines has been collected on a relatively small scale, meaning it has not been possible to evaluate, together, the effectiveness of the different brands and types of vaccines in use during a given flu season.

DRIVE collects results of independent studies from several countries and analyses them together. The studies are conducted by the public partners only (without the involvement of the vaccine manufacturers), and reviewed by an independent scientific committee. The results of DRIVE will help all involved in vaccine development to improve the effectiveness of flu vaccines in the future.

The DRIVE network is expanding, and eight new study sites joined the project during the first call last year. The new tender for new associate partners will be opened in February for study sites capable of researching the influenza vaccine. ​

COMBACTE-CARE completes recruitment for major antimicrobial resistance study

COMBACTE-CARE has recruited 2 266 patients to its EURECA study on infections that are resistant to antibiotics called carbapenems, which are considered to be among the most difficult to treat. In a statement, the project said: ‘Excellent collaboration between the central team and the study sites has ensured that the study has run smoothly, and in future will lead to results that have a significant impact on the practice of infectious diseases in Europe and elsewhere.’ Cases of infections caused by bacteria known as carbapanem-resistant enterobacteriaceae (CRE) are on the rise, and are most common in healthcare settings. They are extremely hard to treat (very often the only treatment options are combinations of old, toxic antibiotics) and can be fatal. The EURECA study is investigating the risk factors for CRE infection and things that influence treatment outcomes. The samples collected during the study are now being sent to a central site for analysis.

PHAGO reveals complex role of TREM2 gene in Alzheimer’s disease

Scientists have shed new light on how a gene called TREM2 influences the progression of Alzheimer’s disease in different ways in the early and later stages. The findings, published in Nature Neuroscience, add to our understanding of the disease and have major implications for drug development. The work was funded in part by IMI through the PHAGO project. TREM2 codes for the TREM2 protein, which activates immune cells in the brain called microglia. Microglia play a vital role in the removal of amyloid plaques, the tangled toxic proteins which are a hallmark of Alzheimer’s disease. In this study, the researchers showed that in mice with early signs of plaque deposition (and a functioning TREM2 gene), microglia cluster around small plaques and cause them to disintegrate. In mice lacking a functional TREM2 gene, the microglia were not able to break up the amyloid plaques. This suggests that in early stage Alzheimer’s disease, activating TREM2 could help to prevent the build-up of toxic amyloid plaques.

However, the results of a similar test in mice with more advanced plaque deposition paint a different picture. There, the amyloid plaques grew faster in mice with a functioning TREM2 gene than in mice without it. Further analyses showed that in the microglia, TREM2 also stimulates the production of a protein called ApoE, which is by far the strongest genetic risk factor for developing sporadic Alzheimer’s disease, and is thought to promote the aggregation of amyloid plaques. ‘Our findings indicate that future therapies will need to be applied in a stage-specific manner,’ says Christian Haass of DZNE Munich and Ludwig-Maximilians University, who led the research. ‘Based on the outcome of our study, activation of microglia by TREM2 would be a useful strategy to apply during the early phase of the condition.’ Professor Haass and his colleagues are now working on antibodies that could stabilise the TREM2 protein, increasing its ability to activate microglia.

ADVANCE conference on vaccine benefit and risk monitoring

The ADVANCE project will hold a conference entitled ‘EU ecosystem for monitoring of post-licensure vaccine benefit and risk: From ADVANCE to VAC4EU’ in Brussels, Belgium on 6 March 2019. ADVANCE brings together all major stakeholder groups interested in the post-marketing monitoring of the health benefits and risks of vaccines, and the consortium has demonstrated that the wealth of existing real-world health care data in the EU can be used to generate actionable evidence on vaccine coverage, benefits, and risks. This event will showcase the projects’ outputs; debate whether and how rapid evidence may help in reducing vaccine hesitancy; and present VAC4EU, the association which will implement the ADVANCE blueprint in the post-project phase. VAC4EU will allow EU research organisations to join the community and study network and collaborate in generating high quality and timely evidence on vaccine coverage, benefits and risks.

• Download the agenda
• Register to attend (deadline: 15 February)