Influenza : the Reasons for Low Vaccine Coverage Among Pregnant Women


A study carried out by Béatrice Blondel (Inserm Obstetrical, Perinatal and Pediatric Epidemiology Research Team – Université de Paris) and Odile Launay (CIC Cochin Pasteur – AP-HP) reveals that seasonal influenza vaccine coverage remains particularly low among pregnant women in France (7.4% for the 2015-16 season). Despite risks of severe complications, expectant mothers are often not offered the vaccine during their prenatal monitoring or, if they are, a large majority declines it. The findings of this study have been published in Human Vaccines and Immunotherapeutics.

Since 2012, the French health authorities recommend that all pregnant women be vaccinated against influenza. Data from the scientific literature suggest that they and their newborns run a higher risk of developing severe complications of the disease.

Nevertheless, vaccine coverage of pregnant women in France continues to remain low, with Inserm researcher Béatrice Blondel and her colleagues estimating it at 7.4% for the 2015-16 season. To obtain this figure, the team used data from the National Perinatal Survey – a large-scale study periodically conducted by Inserm in France since 1995 to evaluate the health of mothers and their newborns in addition to medical practices during pregnancy and birth.

Over 12,000 women that had given birth in March 2016 agreed to participate. “The fact that they had given birth in March was relevant for our study because their pregnancy coincided with the ‘flu epidemic and the entire vaccination period, meaning that the vaccination measures were totally applicable to them“, emphasizes Blondel.

The women were interviewed to find out not just whether they had been vaccinated against the disease during their pregnancy, but also which care provider had performed their prenatal monitoring. In addition to estimating vaccine coverage, the researchers analyzed the factors that favor vaccination, as well as the reasons why a large majority of women had not made use of it.


Lack of knowledge and suspicion of vaccination

 An analysis of the sociodemographic characteristics of the study participants reveals that the pregnant women most likely to be vaccinated are aged between 30 and 34, have a higher level of formal education, and are more likely to work in the healthcare sector.

In addition, those whose main care provider during the pregnancy was a general practitioner also have a higher level of vaccine coverage. “The problem in France is that the principal professionals responsible for prenatal monitoring, namely the OB-GYNs and midwives, have not taken up this question and have not systematically incorporated vaccination in the prenatal monitoring process”, specifies Blondel.

The study suggests that effective interventions should be conducted to raise awareness of influenza vaccination among medical professionals and pregnant women. Indeed, only one quarter of the mothers interviewed said that they had been offered the vaccination during their prenatal monitoring, which was then declined by 70% of them. Targeted campaigns to remind pregnant women that they are one of the populations at risk and to incite care providers to offer the vaccine could have a positive impact. In this context, given the numerous and widely-dispersed care providers involved in prenatal monitoring, the professional associations could play a decisive role in these interventions.

“Women also need to be made aware of the known benefits of the vaccination. While vaccine hesitancy is particularly strong in the French population as a whole, the principle of precaution in regards taking medication is very firmly rooted in the behavior of pregnant women. The cumulation of these two attitudes helps to explain the low vaccine coverage. Nevertheless, the inclusion of pregnant women in the 2019 national vaccine campaign should encourage improved adherence of health professionals and these women”, concludes Blondel.

20 YEARS OF INSERM PRIZES: Honoring science for health

Portraits des prix Inserm 2019


This year marks the 20th annual Inserm Prize ceremony, to take place on Tuesday December 10 at Collège de France in celebration of six researchers and engineers whose achievements have helped raise the level of scientific excellence at the Institute, in the service of health for all.

“By paying tribute to its talented scientists for the 20th year running, Inserm celebrates the passion and commitment of the women and men who represent the diversity and excellence of our research, in the service of health for all”, declares Gilles Bloch, Inserm Chairman and Chief Executive Officer.

The Inserm Grand Prize this year is awarded to Éric Gilson, whose research has contributed to major advances in the biology of aging, and who is Director and founder of the Institute for Research on Cancer and Aging in addition to Scientific Coordinator of the Inserm AgeMed research program.

Éric Gilson, Inserm Grand Prize

From a very early stage in his career, Éric Gilson has been passionate about the knowledge frontier in chromosomes. His desire to question scientific dogmas has led him to play a decisive part in elucidating the role of telomeres – repeated DNA sequences found at the extremity of the chromosomes. It is to him that we owe the discovery of the protective protein caps that contribute to chromosome stability. Far from restricting himself to fundamental research, Gilson wanted to link his research field to more general issues related to the biology of aging and cancer. In 2012 he founded the Institute for Research on Cancer and Aging in Nice, with the support of Inserm, CNRS and Université de Nice. He continues to direct this institute, which was one of the first in the world to combine cancer and aging in a common biology and which continues to attract high-caliber researchers from France and abroad. Since its launch in 2016, Gilson is also the Scientific Coordinator of the Inserm research program AgeMed, which brings together researchers from all walks of life to study the aging process in its entirety.


Mathilde Touvier, Research Prize

The Research Prize is awarded to researchers, lecturer-researchers and clinician-researchers whose work has made a significant impact on fundamental research, clinical and therapeutic research and public health research. Inserm Research Director at the Center for Research on Epidemiology and Statistics, Mathilde Touvier leads the Inserm Nutritional Epidemiology Team. There she has contributed to the development of the Nutri-Score nutritional labelling, rolled out in France and various European countries, which represents a true step forward in the promotion of good health. She also coordinates the NutriNet-Santé study – the world’s first nutrition research cohort – in which she leads research to shed light on the link between the consumption of ultra-processed products and the development of cancer and cardiovascular disease.

Michel Sadelain, International Prize

In line with the Institute’s long-standing tradition of international cooperation, the International Prize rewards the careers of researchers established abroad. This year it is awarded to Michel Sadelain, Director of the Center for Cell Engineering
at the Memorial Sloan-Kettering Cancer Center in New York. Fascinated by the future of gene transfer, this physician-researcher has spent twenty years developing a revolutionary cancer-fighting technique that improves the efficacy of T cells in immunotherapy procedures. His principle? Take the patient’s own immune cells, manipulate their genetic heritage, and then inject them back!

Jean-François Delfraissy, Prize of Honor

The Prize of Honor acknowledges the career of an eminent scientific figure. Jean-François Delfraissy, President of the French National Consultative Ethics Committee (CCNE), is awarded this prize for his research and discoveries in infectious diseases, in addition to his commitments to fighting AIDS and to its patients. Implicated from the late 1980s in the fight against the HIV epidemic that shook the medical world, he set up the Virus, Neuron and Immunity research unit at Kremlin-Bicêtre Hospital and created the first AIDS patient cohorts, bringing fundamental and clinical research together. At the helm of ANRS from 2005 to 2016, Delfraissy was also Director of the Aviesan Immunology, Inflammation, Infectiology and Microbiology Multi-Organization Thematic Institute, and leader of the Ebola Task Force in 2014.

Hervé Chneiweiss, Opecst-Inserm Prize for Social Impact

With this prize, the Institute rewards efforts to promote research and the ability to be truly in dialogue with societal expectations and citizens’ health questions. Chairman of the Inserm Ethics Committee, Hervé Chneiweiss is renowned for his work on astrocytes, whose functioning he has elucidated. His research, at the frontier of neurology and genetics, very quickly led him to develop an interest in bioethics and the place of science in society. Adviser to the cabinet of the French Research Minister from 2000 to 2002, his responsibilities involved the initial revision of the bioethics laws. Both Inserm and the French Parliamentary Office for the Evaluation of Scientific and Technological Options (Opecst), of which he was a member of the Scientific Advisory Board, wish to pay tribute to the career of an individual who, elected Chairman of the Unesco International Bioethics Committee in July, now upholds this commitment beyond our borders.

Chiara Guerrera, Innovation Prize

Research is also comprised of and supported by engineers, technicians and administrative staff: the Innovation Prize is dedicated to them. Originally from Italy, Chiara Guerrera joined the brand new university proteomics platform of the Necker federative research structure (Inserm/APHP/Université de Paris) as a Research Engineer in 2006. She worked on developing this young structure into a very high level platform that not only offers technical assistance in line with the researchers’ needs but also the appropriate strategic and methodological support. Her team has participated in identifying biomarkers that are decisive in the understanding of serious diseases such as cystinuria and cystic fibrosis.

Reprise de la campagne de vaccination contre la grippe


D’après la Fédération des pharmaciens d’officine (FSPF), plus d’un million de personnes en France s’étaient déjà faites vaccinées contre la grippe au 1er novembre 2019, deux semaines après le lancement de la campagne annuelle. Avec le réseau Sentinelles et le projet Grippenet, l’Inserm participe activement à la surveillance des apparitions de symptômes grippaux sur le territoire français.

Entamée le 15 octobre, la campagne de vaccination contre la grippe 2019 continue de s’étendre, les pharmaciens dénombrant déjà plus d’un million de doses administrées au 1er novembre sur les 4 millions de doses délivrées. Dans notre dossier d’information sur la grippe, nous rappelons que c’est 2 à 8 millions de personnes qui sont touchées chaque année par le virus de la grippe, également appelé Influenzavirus.

Fatigue, fièvre, toux, « nez qui coule » : si les symptômes sont en apparence similaires à ceux d’un rhume ou d’une rhinopharyngite, la grippe est plus éprouvante que les autres pathologies fréquentes de l’hiver. Mutant chaque année, l’Influenzavirus peut même s’avérer mortel, notamment pour les enfants, les personnes âgées et les personnes fragiles, faisant en moyenne 5000 morts chaque année.


Sous haute surveillance à l’échelle mondiale, l’épidémie annuelle de grippe l’est aussi en France, sous la coordination de Santé publique France. C’est dans cet objectif que, depuis 1984, l’Inserm participe à la tenue du réseau Sentinelles, en partenariat avec la faculté de médecine de la Sorbonne. Plus de 1400 médecins généralistes et pédiatres libéraux, tous volontaires et répartis sur le territoire métropolitain, fournissent les données de leurs consultations afin d’établir un bilan statistique et géographique des tendances épidémiologiques. Les indicateurs ainsi fournis permettent d’évaluer l’incidence de nombreuses pathologies de manière hebdomadaire. On sait ainsi que les symptômes grippaux sont encore légers en cette fin de mois de novembre, même si certaines tendances se démarquent dans les Cévennes, dans l’Artois et dans le bocage mayennais.

Par ailleurs, les chercheurs et les professionnels de Santé peuvent aussi se reposer sur les données de surveillance fournis par le projet Grippenet. Mis en place en 2012 par le réseau Sentinelles, c’est un projet de surveillance épidémiologique permettant à tout le monde de participer en ligne, anonymement, en renseignant les symptômes dont ils pourraient souffrir d’une semaine sur l’autre. Cela permet aux chercheurs de l’Inserm et de Sorbonne Université de suivre l’évolution d’individus pouvant monter des symptômes grippaux sans pour autant avoir été consulter un médecin généraliste.

Bruno Lina, chercheur Inserm au Centre international de recherche en infectiologie (CIRI) de Lyon déclarait pour notre dossier que « [les] outils de lutte actuels ne suffisent pas à éliminer le problème de santé lié à la grippe. Nous avons un vrai besoin de connaissances dans tous les domaines ». Le réseau Sentinelles, avec l’appui du projet Grippenet, sont des outils importants pour les chercheurs désireux d’enrichir les connaissances épidémiologiques sur l’Influenzavirus et, entre autres, d’améliorer les mesures de prévention et l’efficacité des vaccins contre la grippe.

Towards a Drug to Combat a Severe Intestinal Disease in Children, Immunocompromised Patients

3D structure of the enzyme with the molecule AN3661 shown against the background of the intestine of an immunocompromised mouse infected with Cryptosporidium. ©Fabrice Laurent and Christopher Swale.

Researchers from Inserm and INRA working in the teams of Mohamed-Ali Hakimi (Institute for Advanced Biosciences – Inserm U 1209 / CNRS JRU 5309 / UGA) and Fabrice Laurent (INRA) have recently discovered a new candidate drug to control cryptosporidiosis, a severe intestinal disease in children, immunocompromised patients, and young ruminants. Beyond this disease, their research represents an opportunity to discover new therapeutic avenues for related infections, such as toxoplasmosis and malaria. Their findings have been published in Science Translational Medicine.

Cryptosporidiosis is a diarrheal disease caused by Cryptosporidium, a microscopic parasite that develops in the intestine of numerous mammals – notably humans. This intestinal parasite is mainly spread through contaminated drinking or pool water, where it can survive for several days in the presence of chlorine, or through contact with infected animals. Over the past 20 years, infection with Cryptosporidium has been recognized as a common cause of waterborne disease in humans. According to a recent study by the US Centers for Disease Control and Prevention (CDC), the number of Cryptosporidium epidemics is even on the increase. In humans, it causes acute and sometimes fatal diarrhea in the most vulnerable populations, including young malnourished children and immunocompromised patients (for example, those infected with HIV). The therapeutic arsenal is currently very limited and in some cases ineffective in eliminating this parasite.

This study conducted by the researchers from Inserm and INRA reveals the discovery of a candidate drug called AN3661, which drastically reduces not just Cryptosporidium infection but also that of Toxoplasma, the parasite responsible for toxoplasmosis.

The study teams have revealed the mechanism of action of this molecule by elucidating the three-dimensional structure of its target, called CPSF3, in Cryptosporidium. AN3661 binds to the heart of the enzyme CPSF3, thereby preventing the maturation of the messenger RNA, a process essential to the parasite’s survival. Preclinical tests using an animal model show remarkable efficacy in vivo with single-dose treatments of the infection in immunocompromised or baby mice.

This major discovery paves the way for new therapeutic strategies and innovations to fight not just cryptosporidiosis but also other related infections, such as toxoplasmosis and malaria.

Operation Cortex: an Escape Game by Inserm

© Emeraude Escape

Inserm’s first ever escape game, Operation Cortex, an immersive experience to raise awareness of health research, opens its doors to the general public on November 15. This new public interaction format fulfils the institute’s desire to promote scientific culture and enable visitors to discover its laboratories.

For more than fifty years, Inserm has worked daily to improve individual health through science. It participates in bringing knowledge and scientific culture to all citizens, with the use of innovative formats.

In Operation Cortex, players are transported to the year 2064, to a future in which Inserm scientists have succeeded in developing an artificial brain dedicated to the study of sensory perceptions, sleep, diseases, etc. A tool that offers exceptional prospects for the advancement of knowledge. But when they visit the laboratory behind this scientific feat, the players will find that things will not go entirely to plan… they will need to work their brains hard if they are to get out!

For Inserm Chairman and Chief Executive Officer, Gilles Bloch: “It is important that the public visit our laboratories so they see for themselves the work being done on a daily basis in health research, so they can see the modern methods and cutting-edge technologies being developed. This escape game is our way of interacting with the public in a bold and immersive way. “

Operation Cortex lasts 45 minutes and is open to everyone from 10 years of age (children must be accompanied by adults). Following the game, participants have the opportunity to dialog with the Inserm researchers in charge of hosting them. In Paris, a number of daytime and evening sessions have already taken place in four laboratories this month. Outside Paris, sessions will be held in various regional cities starting from January 2020. Participation is free, but participants are required to sign up first. We will publish the various opening dates on our Facebook page and website as and when they become available.

View our teaser video and poster

In Paris, Operation Cortex will be hosted by:

Scientific and Organisational Committee: Thierry Galli, Inserm Research Director and Director of the Institute of Psychiatry and Neuroscience of Paris; Nicolas Ramoz, Inserm researcher and molecular neuropsychiatry specialist; Diana Zala, Inserm researcher and cellular neurobiology specialist; Armelle Rancillac, Inserm researcher and neurobiologist; Elisabeth Davenas, General Secretary, Institute of Psychiatry and Neuroscience of Paris; Patricia Oliviero, Communications Officer, Brain & Spine Institute; Thu Mai Nguyen, Scientific Project Manager, Biomedical Ultrasound ART; Cyrille Mahieux, General Secretary, Paris-Cardiovascular Research Center; Muriel Delacroix, Administrative Manager, Paris-Cardiovascular Research Center.

Operation Cortex design and production: Emeraude Escape

Type 1 diabetes : a research update from Inserm

Pancreatic islets seen under the microscope ©François Pattou/Université de Lille

From the discovery of insulin in 1921 to the first ever pancreas transplants in the late 1960s, the recent history of type 1 diabetes research has brought scientific and medical advances which have transformed patient prognosis and quality of life.

In France and worldwide, researchers continue to strive to improve the management of patients. Here at Inserm, eleven teams distributed among nine units contribute their own endeavors. Their work primarily involves the characterization of pancreatic cells and improving knowledge of the disease (risk factors, genetic susceptibility, pathophysiological mechanisms) and its complications.

One of these teams, based in Lille, is exploring islet transplantation, a promising technique discussed in a new publication in Diabetes Care[1] and in an update in The Lancet[2]. Other very interesting avenues currently being explored include immunotherapy and the development of artificial pancreases.


I. Type 1 diabetes research at Inserm

The teams at Inserm are involved in various collaborative projects to bring about advances in the treatment of type 1 diabetes. The findings of some already look promising.

  • EXALT (2014-2019)[3], with the participation of Christian Boitard’s Inserm team at Institut Cochin, was a project that aimed to evaluate the effects of an innovative immunotherapy on type 1 diabetic patients. Based on the administration of a peptide, the objective of this immunotherapy was to modify the autoimmune reaction directed specifically against the pancreatic beta cells. The first part of the project used experimental models to demonstrate that there is indeed an effect on the autoimmune reaction of diabetes. The results of the phase 1b clinical trial are currently being analyzed.


  • Hypo-RESOLVE (2018-2022)[4], a European project currently being conducted by Éric Renard in Montpellier (Inserm 1191/JRU 5203), aims to consolidate scientific knowledge on hypoglycemia. The idea is to create a permanent clinical database, conduct studies to further elucidate the underlying mechanisms of hypoglycemia and perform a series of statistical analyses to define its prediction factors and consequences. In addition, the researchers also wish to calculate the financial cost of hypoglycemia in the countries of Europe.


  • Artificial pancreas: Éric Renard and his colleagues have conducted research in collaboration with the University Of Virginia (Charlottesville, VA, USA) to create an artificial pancreas. The algorithmic system developed has been incorporated in the Tandem Control-IQ device, with a view to its commercialization (see photo below). Currently being trialed in 120 type 1 diabetic children in France as part of a national hospital-based clinical research program, interim-analysis data indicate that normal blood glucose levels are maintained for 71% of the 24-hour period, with a significant reduction of the time spent with abnormally high or low blood glucose levels. While its name might be confusing, the artificial pancreas is not actually a fake organ that will be transplanted into the patient but rather a technological device made up of three key elements: a sensor, a pump and an algorithm. The subcutaneous sensor continuously measures the patient’s blood glucose. The pump administers insulin through a fine cannula placed under the skin. The challenge of the artificial pancreas currently lies in the third part of the system: the algorithm capable of automatically making the link between the sensor and the pump.


  • Raphaël Scharfmann’s Inserm team at Institut Cochin has over the previous decade produced new cell models of type 1 diabetes, in the form of human beta-cell lines. His team is now seeking to develop innovative therapies based on the use of stem cells.

II. An alternative to insulin

a) Insulin-producing islets

In this context of ongoing innovation, the allotransplantation of islets of Langerhans, these specialized cells in the pancreas that produce insulin, has also emerged as a particularly interesting therapeutic avenue. Over the previous two decades, François Pattou, Marie-Christine Vantyghem and Julie Kerr-Conte in Inserm unit 1190 Translational Research in Diabetes, and their colleagues in the surgical and endocrinology/diabetes departments of Lille University Hospital have been developing this approach, in which over 50 people have received transplants.

Beyond the indisputable benefit for patients, their research is a perfect illustration of the contribution of translational research and of how laboratories and hospitals can join forces to improve knowledge and treatment of the disease.

In France, 3.9 million people have diabetes, around 5% of whom have type 1. This form of the disease is caused by a deficiency of the hormone insulin, which leads to prolonged high blood glucose levels (hyperglycemia).[5]  Type 1 diabetes is considered to be an autoimmune disease because it is caused by a dysfunction of the immune cells that identify the pancreatic islets of Langerhans as cells foreign to the body, and destroy them. These islets are therefore no longer able to fulfill their usual role of insulin production.

b) Principle of the transplant

At present, the reference treatment for type 1 diabetes is based on the administration of insulin, either by multiple daily subcutaneous injections or by pump. Patients have the use of human insulin analogs  that make it possible to restore and maintain normal blood glucose levels.

Nevertheless, some patients find that their blood glucose levels are not properly controlled with this treatment, despite strict observance of dietary and therapeutic advice. Severe complications can then develop. Poorly-controlled blood glucose can be harmful to the organs, affecting the heart and vessels to begin with, but also the small arteries that supply the kidneys, the nerves of the lower limbs, and the retina.

Alongside the technological approaches (insulin pump, glucose sensors and – soon – the closed-loop pump), the biological approach involving the transplantation of islets represents an essential step for diabetes research. By making it possible to restore almost physiological insulin secretion, the transplantation of insulin-secreting cells transforms the lives of patients, who until now had run out of all therapeutic options.

The principle of islet transplantation or diabetes cell therapy is to replace the destroyed pancreatic cells in order to restore regulated insulin production. This makes it possible to normalize patient blood glucose control and even discontinue the use of insulin. “Islet transplantation is offered to two types of patient: those who have very unstable, often longstanding, type 1 diabetes, particularly with severe hypos and/or hypo unawareness, and kidney transplant patients who are already taking immunosuppressants which then just need to be adjusted”, points out Vantyghem.

II. Two decades of transplants

a) The early days of islet transplantation

In type 1 diabetic patients whose renal complications justify kidney transplantation, the simultaneous transplantation of a whole pancreas has for a long time represented the most effective therapeutic alternative to insulin. A trend which could nevertheless reverse in coming years, given the non-negligible risks associated with the procedure. The pancreas is a fragile organ, difficult to remove from donors.

The injection of islets – i.e. only the useful, insulin-secreting, cells – is a procedure that is less complicated but equally as effective.  “Pancreas transplantation is an effective procedure but carries a high risk of sometimes severe complications. In the beginning, pancreas transplantation did give better results in terms of blood glucose control. But great progress has been made in islet transplantation, which is also less risky, and can now be offered to patients who would not tolerate a pancreas transplant”, specifies Pattou.

The first tests and clinical trials of this technique date back to the late 1960s. However, the major turning point in the history of islet allotransplantation is considered to be the year 2000. This was the year in which Canadian researchers published the results of a clinical trial in the New England Journal of Medicine[6]. Thanks to pancreatic islet transplantation, seven type 1 diabetic patients became fully insulin-independent one year later, no longer requiring their insulin injections.

 “After the year 2000, research into this procedure took off, with other successes reported worldwide – particularly by our group. The problem is that very few studies went on to focus on patients over the long-term – and we are the first to present the results of a 10-year study”, highlight Pattou and Vantyghem.

b) 10 years of follow-up

The new study, published in Diabetes Care by Pattou, Vantyghem and their teams, retraces the paths of 28 patients who had received an islet transplant between 2003 and 2012, half of whom had already received a kidney transplant for renal failure.

Prior to this research, various groups had already published results on the outcomes of islet transplant patients, but none had gone beyond a follow-up period of five years. All highlighted the clinical benefits for the patients and their improved quality of life. However, in the absence of rigorous longer-term follow-up, questions remain unanswered. Are the benefits of islet transplantation maintained beyond five years? What about the complications associated with taking immunosuppressants?

The protocol for performing islet transplant surgery has been established over the previous two decades by the team in Lille, drawing attention not just to the quality but also to the quantity of the islets used. “We chose to start by transplanting a large number of islets. If they come from a particularly robust pancreas containing many islets, one transplant can be enough. However, this situation is exceptional and one or two additional transplants are generally needed. The particularity of our program is to rapidly schedule new transplants, independently of the results of the first, to give patients every chance of achieving normal insulin production”, explains Pattou.

Islet transplant: a few words about the procedure

The isolation of islets now takes place in a number of specialist laboratories, in Lille by Kerr-Conte’s team and also in Geneva, Paris, Montpellier and Strasbourg, from pancreases taken from donors with brain death.

The preparation is then injected into the liver through a small abdominal incision or percutaneously in order to infuse the islets in the portal vein of the liver. The main risk of this procedure is thrombosis, meaning that patients must be given anticoagulants.

Pancreatic islets seen under the microscope – François Pattou/Université de Lille

c) Promising results

As part of their study, the patients were seen at the hospital at least once a year for ten years to check the condition of the transplant. The majority of the patients were seen quarterly. At each visit, the patient’s clinical situation, blood glucose control, exogenous (originating from outside the body) insulin requirements and the diabetic and treatment-related complications were evaluated.

The research team had chosen to study, as primary endpoint, insulin independence with normal blood glucose levels. The doctors wanted to determine the proportion of their patients able to maintain good blood glucose control, without the exogenous provision of insulin. The study highlights that this is the case after five years for half of the 28 patients, and after ten years for almost one third (28%). These findings are similar to those obtained with whole-pancreas transplantation.

The researchers have also shown that 80% of the patients had a transplant that was still functional after five years, with no major hypoglycemic events. After ten years, this remained the case for two-thirds of them. Finally, there was no significant deterioration in kidney function, despite the possible renal toxicity of the immunosuppressants, which was probably compensated for by precision dose adjustment and the excellent blood glucose control obtained in the majority of the patients.

These results show that such a procedure can considerably improve the blood glucose levels of uncontrolled type 1 diabetic patients, protect them from the potentially fatal risk of severe hypos or hypo unawareness, avoid the serious complications associated with the disease and significantly improve their quality of life.

In order to understand why the procedure has greater long-term efficacy in some patients rather than others, several avenues are emerging. “It would appear that there is a signal in favor of women, with some experimental elements showing that the presence of estrogens is favorable to the islets’ survival. The patients with the best long-term results are particularly those who had regained good blood glucose control just after the transplant. To optimize this, attention needs to be paid to the quality and quantity of the islets initially transplanted”, state Pattou and Vantyghem.

An application to obtain reimbursement status for islet transplantation from France’s National Authority for Health is in progress. The response is expected for 2020.


III. What does the future hold?

Various difficulties remain, notably the potential immunological rejection of the transplanted cells, and the limited number of human insulin-secreting cells available for transplant given the current shortage of donors.

Indeed, to avoid rejection of their transplant, patients are required to take immunosuppressant treatment which has a certain number of side effects. Several teams are currently working on finding new solutions to avoid this phenomenon. In addition, in order to develop alternatives to human donors, a number of teams worldwide are currently conducting studies that aim to produce islets from pluripotent stem cells, and successfully transplant them[7].

These two issues could be resolved through a joint approach in order to disseminate diabetes cell therapy more widely: “The Holy Grail would be to produce islets from stem cells in the laboratory and then transplant them inside capsules of biomaterials that shield them from the immune system”, highlights Pattou.

In addition, various research is ongoing to develop fully autonomous artificial pancreases. At present, the blood glucose control obtained with these external devices remains inferior to that obtained with the transplant and the “biological” restoration of insulin secretion.  “These approaches nevertheless prove complementary and are offered in accordance with the profile of each patient”, specifies Vantyghem

The publication of the islet transplantation results after 10 years is a significant new step in the treatment of type 1 diabetes. These findings show that the cell therapy can work over the long term if sufficient islet mass is transplanted.   This research opens up very interesting avenues for the various teams working on new sources of insulin-secreting cells, especially those produced from stem cells and which will make it possible to compensate for the shortage of donors.

IV. What the patients say

Michèle, age 61, transplanted 14 years ago

©Alain Vanderhaegen – Communication Division of Lille University Hospital

“Your daughter won’t survive beyond the year 2000. She will never marry or have children”.  That was how an unsympathetic doctor informed Michèle’s mother that her child had type 1 diabetes. At the time, Michèle did not really understand what was happening. This was in the 1970s and for her the year 2000 was very far off. She did not feel ill. Yes, she had lost a lot of weight recently but she did not feel unwell.

Then, all of a sudden, everything changed. Her resulting stay in hospital, being the only child in a ward of elderly people suffering from major diabetes complications, including amputations, was genuinely traumatic. “Psychologically, it was very tough. I lived a life of untruths, to avoid other people’s questions”, she explains.

Administering the treatments was difficult. The needles had to be sharpened, the syringes boiled and the insulin injected with a constant feeling of shame, a desire to hide. Life went on for Michèle, she held on. She met her husband Jacques, had a son, both of whom support her. From a young age, her son knew what to do when his mom had a hypo, he knew to get sugar from the cupboard when it was needed.

But her severe hypos became increasingly frequent. Some days, up to five or six in succession, leaving Michèle and her loved ones exhausted. Her diabetes specialist, having met the Lille teams at a conference, decided to refer her for islet transplantation. It took her one year to decide to take the plunge, which she did in 2006. She then had three grafts in quick succession. Immediately after the third, Michèle was able to discontinue her insulin injections.  “The fact that the cells come from deceased donors bothered me. I was also afraid that the transplant would change me. In fact, it has changed my life but I’ve stayed the same, except that these three people are always with me. That shadow will never go away. Progress in transplants using stem cells would be a major step forward”, she emphasizes.

It has been 14 years now since Michèle stopped using insulin, since she has been taking immunosuppressants every day, with no major side effects. For both her and her loved ones, it is a liberation. “I’m a free woman once more – my husband and I can do things independently again. Sometimes I worry about the aging of the transplant, as going back would be unthinkable”, she says.


Carole, age 60, transplanted 4 years ago

©Alain Vanderhaegen

At 14 years of age, Carole was a freshman at boarding school. An experience that she did not enjoy, especially since she could not stop fainting. However, when she changed schools, things seemed to improve. She felt good, and no longer gave her fainting a second thought. Until a medical visit that revealed sugar in her urine, followed by a blood test confirming the diagnosis of type 1 diabetes.

Back at school, after a month in hospital, she was the subject of a lot of attention. “I could say anything I wanted in class, because people would say: it’s not her fault, poor thing, she’s diabetic.  So I made the most of it, I had fun”, she explains.

She tolerated her treatment well, ate more or less normally, got her high school diploma and became an elementary school teacher. At work, she always had bottles of orange juice with her in case of hypos.

But those hypos became increasingly severe, encroaching on her daily activities and deteriorating her quality of life. “When giving birth to my daughter, the doctors did not take my diabetes into account. I had a pulmonary edema and was hospitalized elsewhere. I didn’t see my baby for two weeks, so I went on hunger strike so that they would let me see her. When I left the hospital, I had a hypo one morning. All of a sudden, I couldn’t remember that I had a daughter – I’d forgotten her. Had I been alone, I would have been capable of going out and leaving her behind”, she says.

One day, a friend told her about the islet transplants in Lille which he had heard about on the radio. Carole discussed it with her diabetes specialist who promised to look into it. In the end, it was Carole who found the contact details of the team herself.

Transplanted in 2015 and 2016 on three occasions, Carole is keen to make the most of her life. She has been insulin-independent since the second transplant. Five years later, she continues to tolerate the immunosuppressants well, which she never forgets to take. Her hypos have stopped. She can now drive, do sport, go for walks by herself without having to keep her husband informed. “I can even eat biscuits when my family makes them. But I’m so used to not eating sugar that I actually don’t like it. The transplant changed my life at a time when I was no longer doing anything by myself. These islets are my friends, I’ve given them their own name and I celebrate their anniversary”, she smiles.


Béatrice, age 54, transplanted 1 year ago

©Alain Vanderhaegen

The adolescence of Béatrice was disrupted by the discovery of her diabetes. Originally from the countryside near Rennes, no-one she knew had heard of the disease until her diagnosis at the age of 11. It was difficult to begin with: at school, no-one made the effort to understand her situation. She was obliged to eat in the canteen kitchen and often found herself alone in the school yard. Her insulin injections improved things a little, although there were side effects, particularly weight gain, with each dose increase. Béatrice also suffered from discrimination, which continued into her professional life.

Over the years, new technologies emerged to help patients like Béatrice control their blood glucose better, such as insulin pumps with automatic shut-off and sensors that continuously monitor blood glucose. Nevertheless, there were also disadvantages: her hypos would trigger an alarm at any time of the day or night. “It was very difficult to live with. When I had the transplant my husband said that we could finally get some sleep“. Our quality of life improved markedly”, she emphasizes.

It was when reading an article in the journal of the French Association of Diabetics (AFD) that Béatrice discovered islet transplantation. She was tired, she had just lost her job. “I had the impression that I’d reached the end of the road, I needed a new solution in order to survive. Quite simply, to continue to live. As I was reading the article, I had the immediate feeling that the procedure was for me“, she explains.

It took two years before she was able to convince her diabetes specialist to refer her on, and that she was finally able to meet the Inserm-Lille University Hospital team. At the end of 2018, Béatrice received three transplants and became insulin-independent very soon afterwards. “For me the transplant was a huge gift. Out of respect for the donors, I need to keep fighting. I want to keep them alive, I call them my little angels”, she explains.

Although the immunosuppressants are not without their side effects, notably pins and needles in the legs, Béatrice acknowledges that they are in no way near as bad as the complications related to her type 1 diabetes. “My diabetes was always on my mind, I had the impression that my life revolved around it. We’ll see how I get on, and how the transplant holds up over the next few years, but right now I’m optimistic. For the first time in a long time, I have hope”, she says.


Islets of Langerhans: the cells of the islets of Langerhans (or pancreatic islets) are endocrine cells of the pancreas whose primary function is to produce insulin. The islets of Langerhans are complex micro-organs disseminated in the exocrine pancreas.

Allotransplantation: the most common form of transplantation, in which the donor and recipient are the same biological species but strangers to each other.

Xenotransplantation: transplantation in which the graft comes from a biologically different species – for example, pigs.

Pluripotent stem cells: cells able to multiply infinitely and differentiate into the various types of cells that make up an adult organism.



[2]Advances in β-cell replacement therapy for the treatment of type 1 diabetes”.

Vantyghem MC, de Koning EJP, Pattou F, Rickels MR.

Lancet. 2019 Oct 5;394(10205):1274-1285.




[6] Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus Using a Glucocorticoid-Free Immunosuppressive Regimen, New England Journal of Medicine, July 2000.

[7] Https:// (only available in French)

A Vaccine to Overcome Immunotherapy Resistance


For patients with metastatic cancers such as those of the lung or bladder, or melanoma, immunotherapy represents a genuine therapeutic revolution. Unfortunately, it is only effective in 10 to 25% of those eligible to receive it. Researchers from the Cancer Research Center of Lyon (CRCL – Inserm / CNRS / Université Claude Bernard Lyon 1 / Léon Bérard cancer center) and the Léon Bérard and Gustave Roussy cancer centers have shown that a commercially-available vaccine can overcome resistance to immunotherapy. Their study, published in Science Translational Medicine, shows that not only can gastroenteritis vaccines induce the immunogenic death of cancer cells in vitro, but also that combining them with immunotherapy triggers a potent anti-tumor immune response in vivo – where immunotherapy alone had failed.

How can we overcome resistance to immunotherapies, so that as many patients as possible can benefit from these innovations? A team of researchers led by Aurélien Marabelle (Gustave Roussy and Léon Bérard cancer centers), Christophe Caux (Inserm U1052) and Sandrine Valsesia-Wittmann (Léon Bérard cancer center – Inserm UA8) has studied this question. Their idea was to use vaccines to render immunotherapy effective in those cancers in which it has been unsuccessful so far. Then, the aim was to increase the number of patients who could benefit from such therapy in cancers where it has already been shown to be effective.

In this study, our research team looked at pediatric tumors such as neuroblastomas, which are aggressive cancers that do not respond to existing immunotherapies such as anti-PD(L)1 and anti-CTLA4. In our aim to transform how they respond to immunotherapy, we used various vaccines as sources of pro-inflammatory elements because pathogens such as viruses are able to directly stimulate innate immune receptors” explains Marabelle.

Gastroenteritis vaccines

To start with, the researchers tested 14 commercially available vaccines (BCG, Cervarix, TicoVac, etc.) in vitro for their ability to stimulate these innate immune receptors.

Out of the vaccines tested, those used against rotavirus (Rotarix, Rotateq), the virus responsible for gastroenteritis, were identified as having strong pro-inflammatory properties. Unexpectedly, they observed that these vaccines have an oncolytic action – namely the ability to preferentially infect and kill cancer cells in relation to normal cells and induce what is known as immunogenic death.

Vaccine plus immunotherapy – a potent combination

The researchers also conducted in vivo testing of the most pro-inflammatory vaccines using models of neuroblastoma in which the anti-PD(L)1 and anti-CTLA4 immunotherapies are ineffective in humans. This involved injecting these vaccines either systemically or intratumorally (directly into the tumors).

They observed that when the rotavirus vaccines were injected intratumorally, some of the tumors disappeared. When they then administered the vaccine in combination with anti-PD(L)1 or CTLA4 immunotherapies, all of the tumors disappeared.

While the tumors usually do not respond well to either of these treatments used alone, combining them generates a strong systemic antitumor immune response capable of eradicating both injected and non-injected tumors. “Our findings show that the rotavirus strains contained in gastroenteritis vaccines can make usually naturally-resistant tumors sensitive to immunotherapy“, highlights Caux.

The researchers also sought to explain how the rotaviruses exert a stimulant effect on the immune system. They showed that the activation of an innate immune receptor known as RIG-I (retinoic acid induced gene I) was essential for the synergistic effect of the intratumoral rotaviruses with the immunotherapies.

The findings of this study provide a strong scientific rationale in favor of the development of intratumor immunization strategies for immunotherapy-refractory cancers, particularly in pediatric oncology but also in adults,” concludes Valsesia-Wittmann.

This research was supported by the Pediatric Hematology and Oncology Institute (iHOPe), the French League Against Cancer, Inca, the French National Research Agency (ANR) and the patient associations Les Torocinelles, ALBEC and 111 des Arts.

Is physical activity always good for the heart?

International guidelines emphasize the need to be active in order to prevent cardiovascular mortality. Credits : Adobe Stock

Physical activity is thought to be our greatest ally in the fight against cardiovascular disease. But there may be significant variations in its protective effects across a range of different situations, such as regularly playing a sport, carrying heavy loads at work, or going for a walk with friends. These are the findings of a new study led by Inserm researcher Jean-Philippe Empana (U970 PARCC, Inserm/Université de Paris) in collaboration with Australian researchers. The results have been published in Hypertension.

Cardiovascular diseases are the leading cause of mortality around the world, and there is no sign that this trend is declining. However, a large number of premature deaths could be prevented by taking appropriate preventive measures. Among these measures, physical activity is often presented as having multiple benefits, and international guidelines emphasize the need to be active in order to avoid cardiovascular mortality.[1]

But physical activity is a broad concept, and few scientific studies have looked into the differences between various types of exercise may have. This was the focus of the new study published in Hypertension, which was conducted by the research teams led by Jean-Philippe Empana, Xavier Jouven, and Pierre Boutouyrie (Inserm/Université de Paris), in collaboration with Rachel Climie at the Baker Heart and Diabetes Institute, Melbourne, Australia.

“Our idea was to look at whether all types of physical activity are beneficial, or whether under some circumstances physical activity can be harmful. We wanted in particular to explore the consequences of physical activity at work, especially strenuous physical activity such as routinely carrying heavy loads, which could have a negative impact”, explains Empana.

Sport, work, or leisure

The research by Empana and his colleagues was based on data from participants in the Paris Prospective Study III. For ten years, this extensive French study has been monitoring the health status of over 10,000 volunteers, aged 50 to 75 years old and recruited during a health check-up at the Paris Health Clinic (Paris Preclinical Investigations, IPC).

Participants were asked to fill out a questionnaire about the frequency, duration, and intensity of their physical activity in three different contexts: physical activity through sport, physical activity at work (for example carrying heavy loads), and physical activity in their leisure time (such as gardening).

The cardiovascular health of participants was then assessed based on the health of their arteries using cutting-edge ultrasound imaging of the carotid artery (a superficial artery in the neck). This method, known as “echo tracking”, can be used to measure baroreflex sensitivity, a mechanism of automatic adaptation to sudden changes in blood pressure. When this system is impaired, this can lead to major health problems, and a higher risk of cardiac arrest.

Studying the arduous nature of work

In their analyses, the researchers distinguished between two components of the baroreflex: mechanical baroreflex, assessed through the measurement of arterial stiffness, and neural baroreflex, assessed through the measurement of nerve impulses sent by the receptors on the walls of the artery, in response to a distension of the vessel. Abnormalities in the mechanical component tend to be associated with aging-related cardiovascular diseases, while abnormalities in the neural component tend to be linked to heart rhythm disorders that can lead to a cardiac arrest.

The study shows that high-intensity sporting physical activity is associated with a better neural baroreflex. Conversely, physical activity at work (such as routinely carrying heavy loads) appears to be more strongly associated with an abnormal neural baroreflex and greater arterial stiffness. Such activity could therefore be harmful for cardiovascular health, and in particular may be associated with heart rhythm disorders. 

“Our findings represent a valuable avenue of research for improving our understanding of the associations between physical activity and cardiovascular disease. They do not suggest that movement at work is harmful for health, instead they suggest that chronic, strenuous activity (such as lifting heavy loads) at work may be”, highlights Empana

The researchers will attempt to replicate these results in other populations, and explore in greater detail the interactions between physical activity and health. “This study has major public health implications for physical activity at work. We now want to expand our analysis to further explore the interactions between physical activity and the health status of people in the workplace”, concludes Empana.

[1] See the Inserm collective expert review: “Physical activity: Prevention and treatment of chronic diseases”