A brain mechanism involved in mediated learning is identified

Neurone d’hippocampe Crédits: Inserm/Peris, Leticia

Imagine that you are eating a Granny apple under a red parasol on the terrace of a public garden. The next day you eat another Granny apple at home in your kitchen, but soon afterwards find yourself ill. The next time you go back to the public garden, you avoid sitting under that red parasol. While there may not seem to be a link between the parasol and the fact that you were ill, there actually is! This is an example of the mediated learning process, and researchers from INRA and INSERM have just identified the brain mechanism involved in it. Their results, published online on 30 August 2018 in Neuron, show that cannabinoid receptors in the hippocampus play a key role in establishing these types of associations.

Direct learning, which implies a specific link between information and positive or negative consequences, influences our future choices. However, our behaviour is most often guided by mediated learning, which is based on associations between seemingly insignificant information. This explains why we are often put off or attracted by people, places and things we have never directly associated with aversive (or positive) situations, but which were previously encountered along with other information that acquired an aversive or positive meaning. The apple and red parasol case is an example of this.

Receptors, neurons and the brain structure involved in mediated learning have been identified

While the neurobiological bases of direct learning have been thoroughly studied, understanding of mediated learning mechanisms remains rather limited. Researchers from INRA and INSERM began by establishing mediated learning behaviour models in mice in laboratory experiments. They repeatedly and simultaneously exposed mice to an odour (banana or almond) and a taste (sweet or salty) without a particular effect on the animal. They then associated the taste with a gastric malaise (similar to food poisoning). When the researchers later exposed the mice to the odour initially associated with this taste, they observed that the animals specifically avoided this odour, which showed a transfer of the aversive value between the taste and the odour. The scientists were able to demonstrate similar results with light and sound and the transfer between these sensory inputs of an attractive value (by giving the animals a reward), and thereby generalising the phenomenon.

The scientists were able to pinpoint the mechanism in question: the mediated learning process (between an odour and a taste or a light and a sound) involves the hippocampus and a major neuromodulatory system within this brain structure, called the endocannabinoid system. More specifically, this particular form of learning requires the involvement of type 1 cannabinoid receptors (CB1R) in hippocampal GABAergic neurons.

These unprecedented results will help researchers evaluate whether CB1R are also involved in other brain structures during mediated learning. This could lead to new research to understand certain pathologies (schizophrenia or psychosis) in which mediated learning is altered.

Novel brain network linked to chronic pain in Parkinson’s disease

©Inserm/U746, 2011

Scientists have revealed a novel brain network that links pain in Parkinson’s disease (PD) to a specific region of the brain, according to a report in the journal eLife.


The research reveals why a subset of neurons in part of the brain called the subthalamic nucleus is a potential target for pain relief in PD, as well as other diseases such as dementia, motor neuron disease and Huntington’s, and certain forms of migraine.


People with PD often report unexplained pain such as burning, stabbing, aching, itching or tingling sensations that are not directly related to their other PD symptoms. Treatment with deep brain stimulation in the subthalamic nucleus can help with the movement-related symptoms of PD, but recent studies have shown it also reduces pain. The way it does this, however, is currently unclear.


“In this study, we set out to determine whether the subthalamic nucleus is involved in translating a harmful stimulus such as injury into pain, and whether this information transmission is altered in PD,” explains lead author Arnaud Pautrat, PhD Student at University Grenoble Alpes, France.


The team started by using electrophysiology to measure the firing of electrical signals in nerve cells in the subthalamic nucleus of rats given a shock to their back paw. Nerve cells were indeed temporally activated by this stimulation. They also found that the neurons fell into three response groups, showing an increase, decrease or no change in their baseline firing rate.


They next looked at whether these responses caused a change in brain function. Rats with a damaged subthalamic nucleus took much longer to show signs of discomfort than healthy rats. When they expanded their study to rat models of PD, the team found that nerve cells in the subthalamic nucleus had higher firing rates and the responses to pain were bigger and longer than the healthy animals. Taken together, this suggests that dysfunctional pain-processing pathways in the subthalamic nucleus are the cause of PD-related pain.


To understand where the pain signals to the subthalamic nucleus were coming from, the team looked at two brain structures known to be important in relaying damage signals from the spinal cord: the superior colliculus and the parabrachial nucleus. Blocking their activity revealed that both structures play a crucial role in transmitting pain information to the subthalamic nucleus, and that a direct communication pathway exists between the parabrachial nucleus and the subthalamic nucleus. As a result, the team believes this pathway is likely to be involved in the beneficial effects of deep brain stimulation on pain in PD and that these novel insights could help to target stimulation to specific parts of the brain to make it more effective as a pain reliever.


“We have found evidence that the subthalamic nucleus is functionally linked to a pain-processing network and that these responses are affected in Parkinsonism,” concludes senior author and INSERM researcher Veronique Coizet, PhD. “Further experiments are now needed to fully characterise the effects deep brain stimulation on this brain region in our experimental models, with a view to finding ways to optimise it as a treatment for pain caused by Parkinson’s and other neurological diseases.”

An artificial intelligence predicts therapeutic response in patients with advanced rectal cancer treated with preoperative radiochemotherapy

Cancer colorectal humain et les cellules immunitaires. Crédits: Inserm/Galon, Jérôme

The digestive oncology teams from European Georges Pompidou Hospital, Cochin and Ambroise Paré AP-HP, and laboratory “Information Sciences and personalized medicine” of 1138 Unit Research Center Cordeliers INSERM and Paris-Descartes University, have developed an artificial intelligence system that predict therapeutic response to preoperative chemoradiotherapy in patients monitored for rectal cancer. The work, coordinated by Dr. Jean-Emmanuel Bibault of oncology radiotherapy European Hospital Georges Pompidou AP-HP, would propose a conservative treatment rather than full rectal ablation patients complete therapeutic response.

These results thus contribute to the development of more personalized care in oncology. They were the subject of a publication August 22, 2018 in the journalScientific Reports (Nature Review Group) . 

The standard treatment of locally advanced rectal cancer comprises a preoperative chemoradiotherapy followed by surgical resection (removal) full rectum. About a quarter of patients in complete response after chemoradiotherapy they could avoid radical surgery and benefit instead of conservative treatment (surveillance or endoscopic resection) resulting in less sequelae. However, the only way to know whether these patients respond perfectly to chemoradiation currently remains the operation with removal of the entire rectum.

This study, led by Dr. Jean-Emmanuel Bibault, the radiation oncology department of the European Hospital Georges Pompidou AP-HP, Professor Philippe Giraud, the radiotherapy service HEGP and Professor Anita Burgun, head of the laboratory “information Science and personalized medicine” Unit 1138 Cordeliers research Center INSERM and Université Paris Descartes, therefore aimed to develop an artificial intelligence device which predict in advance the patients with a complete response to preoperative radiochemotherapy, to prevent their operation.

The teams have relied on clinical patient data and images radiation scanners. They then used a method of artificial intelligence-type “Deep Learning” (or “deep neural network”) that has been set for identifying patients with complete response to treatment. The “Deep Learning” is part of machine learning methods that model with a high level of data abstraction.

The algorithm developed was then evaluated on patient data already supported at European Hospital Georges Pompidou, at Cochin Hospital and Ambroise Paré Hospital AP-HP. He was accurate in 80% of cases analyzed. 22 of the 95 patients included in the study had a complete response to preoperative radiochemotherapy.

This study shows that the artificial intelligence algorithms type “deep learning” could be used to predict the effectiveness of cancer treatments to further customize the care of patients.

These results may lead to further research to integrate this device into the treatment of locally advanced cancers of the rectum.

Metformin Improves Motor Skills in Patients with Steinert Myotonic Dystrophy, the Most Common Adult Neuromuscular Disease

Cellules musculaire de patient atteint de dystrophie myotonique. Crédits: Inserm/IGBMC

Inserm researchers at I-Stem – the Institute for Stem Cell Therapy and Exploration of Monogenic Diseases – report encouraging results with metformin, a known diabetes drug, for the symptomatic treatment of Steinert myotonic dystrophy. A phase II trial conducted in 40 patients at Henri-Mondor Hospital AP-HP has shown that, after 48 weeks of treatment at the highest dose, patients treated with metformin (versus placebo) gain in motor skills and recover a more stable gait. The results of this trial, which received 1.5 million euros in funding from AFM-Téléthon, are published today in Brain.

Steinert myotonic dystrophy (DM1) is the most common form of muscular dystrophy in adults. Of genetic origin, its prevalence is estimated at 1/8,000, or about 7 to 8,000 patients in France. It affects the muscles, which weaken (dystrophy) and have difficulty to relax after contraction (myotonia) which disrupts the movements (unstable walking for example). It also affects other organs (heart and respiratory system, digestive system, endocrine system and nervous system). To date, this muscular dystrophy does not benefit from any curative treatment.

The findings published in Brain are the result of research conducted for several years at I-Stem. Indeed, thanks to the development of cellular models from pluripotent stem cells, in 2011 Cécile Martinat’s team identified new mechanisms at the origin of Steinert myotonic dystrophy (Cell Stem Cell – March 31, 2011). In 2015, Sandrine Baghdoyan, a research engineer at I-Stem, succeeded in correcting certain splice defects in embryonic stem cells and myoblasts from people with DM1 using metformin, a well-known diabetes drug identified as effective in this new indication thanks to high-throughput screening (Mol.Therapy – Nov 3, 2015).

Encouraged by these results, I-Stem launched a phase II, single-center, double-blind, randomized controlled clinical trial in 40 patients, in collaboration with teams from Henri Mondor Hospital AP-HP, that of Dr. Guillaume Bassez of the Ile-de-France Reference Center for Neuromuscular Diseases, and that of the Clinical Investigation Center coordinated by Prof. Philippe Le Corvoisier. In this placebo-controlled study, metformin was administered three times daily, orally, with a 4-week increase in dose (up to 3 g/day), followed by 48 weeks at the highest dose. The evaluation of treatment efficacy was based on the “6-minute walk” test. At the end of the study, after one year of treatment, patients who received metformin gained an average walking distance of about 33 meters on their initial performance whereas the group receiving placebo remained stable (average gain of 3 meters). This motricity, analyzed in depth using the Locometryx tool developed by Jean-Yves Hogrel’s Hogrel’s Laboratory of Physiology and Neuromuscular Evaluation at the Institute of Myology at the Pitié-Salpêtrière Hospital AP-HP, is closely linked to the fact that metformin improves the overall posture of patients who, in fact, go from walking in an unstable “broad-based” manner before treatment, to a straight, faster and therefore more efficient gait”.

These results demonstrate, for the first time, the efficacy of a pharmacological treatment on motor function in Steinert myotonic dystrophy and, to our knowledge, the therapeutic efficacy of a molecule identified on the basis of the modeling of a pathology with pluripotent stem cells.

Predicting The Response To Immunotherapy Using Artificial Intelligence

Photo by Ken Treloar on Unsplash

A study published in The Lancet Oncology establishes for the first time that artificial intelligence can process medical images to extract biological and clinical information. By designing an algorithm and developing it to analyse CT scan images, medical researchers at Gustave Roussy, CentraleSupélec, Inserm, Paris-Sud University and TheraPanacea (spin-off from CentraleSupélec specialising in artificial intelligence in oncology-radiotherapy and precision medicine) have created a so-called radiomic signature. This signature defines the level of lymphocyte infiltration of a tumour and provides a predictive score for the efficacy of immunotherapy in the patient.     

In the future, physicians might thus be able to use imaging to identify biological phenomena in a tumour located in any part of the body without having to perform a biopsy.  

Up to now, no marker can accurately identify those patients who will respond to anti-PD-1/PD-L1 immunotherapy in a situation where only 15 to 30% of patients do respond to such treatment. It is known that the richer the tumour environment is immunologically (presence of lymphocytes) the greater the chance that immunotherapy will be effective, so the researchers have tried to characterise this environment using imaging and correlate this with the patients’ clinical response. Such is the objective of the radiomic signature designed and validated in the study published in The Lancet Oncology.

In this retrospective study, the radiomic signature was captured, developed and validated in 500 patients with solid tumours (all sites) from four independent cohorts. It was validated genomically, histologically and clinically, making it particularly robust. 

Using an approach based on machine learning, the team first taught the algorithm to use relevant information extracted from CT scans of patients participating in the MOSCATO study[1], which also held tumor genome data. Thus, based solely on images, the algorithm learned to predict what the genome might have revealed about the tumour immune infiltrate, in particular with respect to the presence of cytotoxic T-lymphocytes (CD8) in the tumour, and it established a radiomic signature.   

This signature was tested and validated in other cohorts including that of TCGA (The Cancer Genome Atlas) thus showing that imaging could predict a biological phenomenon, providing an estimation of the degree of immune infiltration of a tumour.  

Then, to test the applicability of this signature in a real situation and correlate it to the efficacy of immunotherapy, it was evaluated using CT scans performed before the start of treatment in patients participating in 5 phase I trials of anti-PD-1/PD-L1 immunotherapy. It was found that the patients in whom immunotherapy was effective at 3 and 6 months had higher radiomic scores as did those with better overall survival.     

The next clinical study will assess the signature both retrospectively and prospectively, will use larger numbers of patients and will stratify them according to cancer type in order to refine the signature.        

This will also employ more sophisticated automatic learning and artificial intelligence algorithms to predict patient response to immunotherapy. To that end, the researchers are intending to integrate data from imaging, molecular biology and tissue analysis. This is the objective of the collaboration between Gustave Roussy, Inserm, Université Paris-Sud, CentraleSupélec and TheraPanacea to identify those patients who are the most likely to respond to treatment, thus improving the efficacy/cost ratio of the treatment.

[1] Results of the MOSCATO study published in Cancer Discovery :

// About radiomics

In radiomics, it is considered that imaging (CT, MRI, ultrasound, etc.) not only reveals the organisation and architecture of tissues but also their molecular or cellular composition. The technique involves the use of algorithms to analyse a medical image objectively in order to extract from it information which is invisible to the naked eye, such as the texture of a tumour, its micro-environment, its heterogeneity, etc. For the patient this represents a non-invasive approach that can be repeated over the course of the disease to follow its progress. 

Mechanism of Repression: Can a Person’s Memories be Altered Without Their Knowledge?

Photo by Christophe Hautier on Unsplash

In recent years, the cognitive neurosciences have shown that it is possible to use conscious effort to alter memories. Researchers from the Inserm Center for Psychiatry and Neuroscience, Sainte Anne Hospital and Université Paris Descartes now show that it is possible to unconsciously alter memories. This experimental demonstration of the unconscious manipulation of memories, which is similar to the psychoanalytical concept of repression, has been published in the journal Cognition.

Researchers have known for several years that by making a conscious effort to suppress a specific memory, it is possible to alter it, i.e. reduce our ability to recall it. This effect is expressed by the deactivation of the cerebral hippocampi, brain structures involved in encoding memory. Can the same be done unconsciously?

Led by Professor Raphaël Gaillard, researchers from the Inserm Center for Psychiatry and Neuroscience, Sainte Anne Hospital and Université Paris Descartes put their expertise in consciousness and unconscious processes to good use to test this hypothesis.

In order to recreate in a laboratory setting the conditions of an unconscious recall mechanism, volunteers learned related word pairs (e.g. candle-champagne, walk-hill), and then were trained, when the first word was presented to them, to either think of the second word in the pair or to avoid thinking about it, according to a visual cue. A similar experimental system had in the past made it possible to demonstrate the alteration of a memory by conscious effort.

The originality of this study lies in the fact that these visual cues giving th e instruction to think of or try to avoid thinking of the second word in the pair were sometimes presented subliminally, i.e. too briefly to access the consciousness. When this occurred, the volunteers had to determine as quickly as possible whether the first word was masculine or feminine. While these cues were not perceived at the conscious level, the researchers revealed an alteration in the capacity to recall the second word.

Consequently, the cue associated with the instruction not to think of the second word decreased the ability to recall that word, and the cue associated automatically with the instruction to think of it increased it. This study therefore demonstrates that it is possible to unconsciously manipulate the memory of a word.

This research opens up new perspectives in the understanding of unconscious psychological phenomena. If, within the environment of a laboratory and a two-hour experiment time, it is possible to demonstrate such a phenomenon of repression, in daily life the repetition of elements altering a memory could have major effects.

More generally, this research once again shows that memory is vulnerable to distortion –and even manipulation– thereby representing a challenge for witness accounts and memories of one’s own life.

A Hormone Produced During Exercise Could Improve Muscle Capacity in the Elderly

© David Monje – Unsplash 

How can we limit age-related decrease in muscle capacity (sarcopenia), which is a major cause of loss of autonomy in the elderly? Researchers from Inserm, Université Toulouse III – Paul Sabatier and the Gérontopôle of Toulouse University Hospital might have found, within the muscles themselves, a formidable ally in fighting this disease: apelin. This hormone, whose production decreases with age, is secreted during physical activity and improves muscle capacity. This research published in Nature Medicine makes it possible to envisage apelin both as a diagnostic tool for sarcopenia and as a solution for its treatment.

In 2016, WHO finally recognized the decrease in muscle capacity –also known as sarcopenia or muscle loss with aging– as a disease. Indeed, maintaining functional capacity in the elderly is essential to preserve their independence and quality of life. Associated with limited mobility, sarcopenia appears to be a primary cause of the progressive loss of autonomy and the development of age-related pathologies (osteoporosis, cardiac and/or cognitive impairment) and as a consequence one of the main reasons for medical institutionalization.

Sarcopenia is the degenerative loss of skeletal muscle mass, quality and strength. Current treatment strategies produce varying levels of efficacy, often associated with side effects. There is also a lack of early diagnosis tools. Physical activity –while presenting the major disadvantage of often being impractical or fruitless in individuals with reduced motor capacity– is often considered to be the most effective approach. In previous studies it was shown that by stimulating activation of the stem cells at the origin of muscle cells, the muscle contraction generated by physical activity helped renew the muscle fibers (myofibers) and improve their metabolism.

The Inserm research team from the Institute of Cardiovascular and Metabolic Diseases, I2MC (U1048 Inserm/Université Toulouse III – Paul Sabatier) in collaboration with teams from the Gérontopôle of Toulouse University Hospital looked at the relationship between these mechanisms and the development of sarcopenia. They identified a hormone, apelin, produced by the contraction of the muscle during physical activity, and which appears to be capable of maintaining and even restoring muscle capacity.

Indeed, when apelin was administered to elderly mice, the researchers saw their muscle capacity improve and their myofibers return to normal. This improvement is thought to be due to the ability of apelin to stimulate both the cellular metabolism in the muscle and the regeneration of myofibers from stem cells.

Finally, the researchers observed that the production of apelin in response to physical activity diminishes with age. According to Philippe Valet, co-director of the study and professor at Université Toulouse III – Paul Sabatier “in the years to come, apelin could be used for therapeutic purposes in sarcopenia because the results of the study in mice show that treatment with this hormone significantly improves muscle faculties. With this research we can envisage apelin both as a tool for the early diagnosis of sarcopenia and as a promising treatment in the fight against age-related loss of function.”

Clinical trials will be conducted from 2019 by the Gérontopôle of Toulouse University Hospital as part of the IHU-Inspire project which focuses on prevention, aging in good health and regenerative medicine.

Maintaining Good Cardiovascular Health Reduces the Risk of Dementia and Cognitive Decline in Older Age

Photo by George Kourounis on Unsplash

Researchers from Inserm at the Bordeaux Population Health Research Center, the Paris Cardiovascular Research Center, the University of Bordeaux and the Three-City Cohort have demonstrated that combining several factors and behaviors beneficial for the heart and maintaining them at optimal levels is associated with a reduced risk of developing dementia and cognitive decline after the age of 65. The researchers used the concept of optimal cardiovascular health as defined by the American Heart Association in its 2020 Impact Goal concerning cardiovascular disease prevention. This study has been published in JAMA.

As part of a new epidemiological study conducted in the largest French cohort, the Three-City Cohort, initiated in 1999 to elucidate the impact of vascular risk factors on cognitive aging and dementia, researchers from Inserm (at the Bordeaux Population Health Research Center and the Paris Cardiovascular Research Center) followed 6 626 adults aged 65 and over in France for a period of 16 years. To date, a number of studies have shown the relevance of a preventive approach in cardiovascular diseases. Given the biological links and the presence of shared risk factors between cardiovascular diseases and dementia, the research team was interested in the benefits of prevention of vascular risk factors on dementia and cognitive decline.

The concept of “optimal cardiovascular health”, as defined by the American Heart Association, is based on 7 parameters which include 4 health behaviors (not smoking, healthy weight, being physically active and a diet in accordance with public health recommendations) and 3 biological components (ideal blood pressure, cholesterol and blood sugar levels without treatment).

While this study has its limits –notably the study population being from an urban environment and the possible variation of the parameters considered – it nevertheless shows that maintaining optimal cardiovascular health (7 parameters at ideal levels) is associated with a major decrease in dementia risk and an attenuation of the associated cognitive decline.

Therefore, each parameter at ideal level is linked to a 10% reduced risk of dementia (and if the 7 parameters are at optimal level, the risk reduction is 70% in comparison with those with none).

If the objective is to achieve optimal cardiovascular health, the study shows that having just one parameter at ideal level is linked to a reduced risk of dementia. Cécilia Samieri, Inserm researcher in charge of the study, specifies: “In practice, this objective appears more realistic, making it possible to reach a larger number of people and therefore have a greater impact. While health promotion is a collective challenge for public authorities and healthcare professionals, it also involves each individual taking ownership of their own health”.

Chronic Malnutrition In Children: A New Gut Microbial Signature

Projet Afribiota à Bangui RCA en avril 2017. © Institut Pasteur de Bangui / JM Zokoué

Chronic malnutrition, usually associated with an inflammation of the small intestine, affects one in every four children under the age of five. It is the leading cause of child mortality in low-income countries and is also responsible for severe stunting. The Afribiota project, led by the Institut Pasteur in Paris, the Institut Pasteur in Madagascar and the Institut Pasteur in Bangui, in collaboration with the University of British Colombia, Inserm and the Collège de France, was set up to advance our understanding of the underlying mechanisms of chronic malnutrition and improve treatment. A first study recently demonstrated microbiota disorders in malnourished children, revealing the existence of a surprising microbial signature in the gut, characterized by the widespread presence of bacteria that are normally found in the nose and mouth. The findings were published in the journal PNAS on the 20th of August, 2018.

Chronic malnutrition affects one in every four children under the age of five worldwide. It claims more than 3 million lives every year and results in impaired cognitive and physical development, especially stunted growth, which can be difficult to overcome.

With traditional treatment, in other words providing affected children with micronutrients, a balanced diet and ample food while treating the underlying infections, we can only correct 30% of growth delays,” explains Pascale Vonaesch, holder of a PhD in Microbiology and a member of the Molecular Microbial Pathogenesis Unit at the Institut Pasteur. “There really do seem to be a number of phenomena that have not yet been elucidated.

Chronic malnutrition is not only linked to a lack of food; it is also associated with immune problems and chronic gut inflammation, the workings of which are not yet fully understood. The Afribiota project, carried out in collaboration with the Institut Pasteur in Paris, the Institut Pasteur in Madagascar and the Institut Pasteur in Bangui, was set up in 2016 precisely to find out more about the underlying mechanisms of these disorders and to develop more effective treatment.[1]

In this first study, the scientists focused on the children’s gut flora, one of their aims being to characterize the bacterial populations that colonize the small intestine in malnourished children.

We know that these children suffer from gut inflammation. The villi in the small intestine in particular become blunted, preventing the intestine from effectively carrying out its role in digestion and the absorption of nutrients,” says Philippe Sansonetti, a physician and microbiology researcher in the Molecular Microbial Pathogenesis Unit, which he leads at the Institut Pasteur. “But we didn’t know to what extent the usual bacterial populations were being altered.

To shed light on this question, the stools and duodenal juice of 400 children living in Antananarivo (Madagascar) and Bangui (Central African Republic), both with and without chronic malnutrition, were analyzed. Bacterial cultures and metagenomic analyses aimed at revealing all the microbial species present were also performed, yielding surprising results.

We expected to see an increase in enteropathogenic bacteria such as Campylobacter, Shigella or even Salmonella in the malnourished children,” comments Pascale Vonaesch, “but we certainly didn’t expect to see oropharyngeal bacteria!” “What also surprised us was the sheer number of these bacteria,” adds Philippe Sansonetti. “We had already observed this type of phenomenon for some inflammatory bowel diseases and colon cancer, but never such large-scale migrations. There are 10 to 100 times more bacteria than in the control patients.

Oropharyngeal bacteria, some of which are known for their inflammatory properties, seem to have literally crossed the barriers that usually keep them in the nasopharynx and the mouth, migrating towards and colonizing the stomach and the intestine. This unusual, large-scale migration was observed in malnourished children from both Madagascar and the Central African Republic, in other words independently of their origins, eating habits and environment. 

The origins and consequences of this microbial signature in the gut, characteristic of chronic malnutrition, are yet to be elucidated, even if initial theories are already emerging. “We know that children affected by malnutrition also often have poor oral hygiene and suffer from repeated colds. So there could be an overgrowth of oral and nasopharyngeal flora which may then be swallowed and, in the absence of effective controls, arrive in the digestive system,” suggests Philippe Sansonetti. “It is important to clarify this information so that we can issue effective prevention messages.

In the long term, this gut microbial signature, together with data from the epidemiological, biological and anthropological research carried out for the Afribiota project, should help identify the causes of chronic malnutrition, facilitate diagnosis and ultimately improve treatment of this global health threat.

The Afribiota project is supported by the Total Corporate Foundation, Odyssey Reinsurance Company, the Institut Pasteur, the Nutricia Research Foundation and the Petram Foundation.
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2018 Ebola Epidemics: What is the Latest in Vaccine Research?

©Inserm/Delapierre, Patrick, 2018

Since July, a new outbreak of Ebola virus disease was identified in the Democratic Republic of the Congo – the second since May.  In an attempt to halt the outbreak, a new vaccination campaign has begun in the affected region of North Kivu. It is against this background that researchers from the consortium PREVAC (Partnership for Research on Ebola VACcination) take stock of advances in Ebola vaccine research in The Lancet and point to the necessity to continue clinical trials.

Since the end of July, the Democratic Republic of the Congo has been facing its second Ebola outbreak this year, following the one in May.  These outbreaks, which can be added to the one of 2017 in the same country, and the widespread outbreak that occurred in Guinea, Liberia and Sierra Leone from 2013-2016, show the extent to which the risk of Ebola re-emergence is real. While no approved treatments or vaccines exist right now, some vaccines are, however, reaching advanced stages of development. Ebola vaccine research must continue because, when combined with effective public health measures, it is an essential element in preventing and responding to future epidemics.

In 2013, Inserm and its Aviesan partners founded REACTing, a multidisciplinary consortium bringing together research groups and laboratories of excellence in order to prepare for and coordinate research to combat the health crises linked to emerging infectious diseases. It was in this context that, Inserm, the National Institute of Allergy and Infectious Diseases and the London School of Hygiene & Tropical Medicine, in collaboration with the health authorities and scientists of four Ebola-stricken countries (Guinea, Liberia, Sierra Leone and Mali) formed the international consortium PREVAC (Partnership for Research on Ebola VACcination) and launched in 2017 a large-scale clinical trial of three Ebola vaccination strategies. The objective of the trial, whose partners also include the universities of Bordeaux and Minnesota, the NGO ALIMA, and three pharmaceutical companies (Janssen Vaccines & Prevention, B.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson; Bavarian Nordic; and Merck Sharp & Dohme Corp., known as MSD outside the U.S. and Canada), is to identify the most promising vaccination strategies for protecting individuals from Ebola.[1]

Two promising vaccines regimens are being trialed as part of PREVAC, including rVSV∆G-ZEBOV-GP which has been used since August 9, 2018, in response to the new epidemic in the Democratic Republic of the Congo. The second, Ad26.ZEBOV and MVA-BN-Filo prime-boost, is also under evaluation in PREVAC. The latter is also being tested in the EBOVAC project, of which Inserm is a partner.

On August 10, 2018, in an article published in The Lancet, PREVAC researchers take stock of Ebola vaccine research. They note that some key questions remain to be studied via various vaccine strategies. Researchers are concentrating on gaining a deeper understanding of the immune response to the Ebola vaccines, the question of the rapidity and durability of the immune response (and therefore the potential protection) in vaccinated individuals, the safety and the ability of the vaccine to trigger an immune response in children, as well as the nature of the responses in people with immunodeficiencies and pregnant women.

According to the PREVAC team, various vaccine strategies and scenarios need to be researched to identify the most effective way to prevent and respond to future Ebola outbreaks.

Post-exposure vaccination, targeted preventive vaccination for people who have come into contact with infected individuals, as well as preventive vaccinations for at-risk populations, such as healthcare and frontline workers, and possibly residents of areas regularly affected by outbreaks, are some of the strategies to be investigated.

Addressing these challenges requires the pursuit of collaborative partnerships centered on Ebola research. It also requires increasing the local population’s trust in the vaccines and vaccination campaigns. Indeed, the adherence of those enrolled and the engagement of the community throughout the clinical trial process is fundamental to success.  Bringing social sciences into clinical research makes it possible to increase the population’s trust and its involvement in the trials.


[1]All the information on the PREVAC clinical trial can be found on the dedicated Inserm page: