An Asthma Vaccine Effective in Mice

coupes de poumon de souris dans un modèle d'asthme

Visualisation au microscope de coupes de poumon de souris dans un modèle d’asthme avec une coloration à l’acide périodique et Schiff montrant une forte production de mucus (violet foncé) et un infiltrat de globules blancs autour des bronches dans le groupe contrôle (gauche) mais pas dans le groupe vacciné (droite). © Dr Eva Conde

Inserm teams led by Laurent Reber (Infinity, Toulouse) and Pierre Bruhns (Humoral Immunity, Institut Pasteur, Paris) and French company NEOVACS have developed a vaccine that could induce long-term protection against allergic asthma, reducing the severity of its symptoms and thus significantly improving patient quality of life. Their research in animals has been published in the journal Nature Communications.

Asthma is a chronic disease affecting around 4 million people in France and 340 million worldwide. Allergic asthma is characterized by inflammation of the bronchial tubes and respiratory discomfort caused by the inhalation of allergens, most often dust mites. This exposure to dust mites and other allergens leads to the production of antibodies called immunoglobulin E (IgE) and type 2 cytokines (such as interleukin-4 (IL-4) and IL-13) in the airways. This leads to a cascade of reactions resulting in hyperresponsiveness of the respiratory tract, overproduction of mucus, and eosinophilia (when there are too many eosinophils, a type of white blood cell, in the airways).

Inhaled corticosteroids are the gold standard for controlling asthma. However, in the case of severe asthma, this treatment is not enough. The use of therapeutic monoclonal antibodies that target IgE or the IL-4 and IL-13 pathways is then required. However, these are costly and require the long-term or even lifelong administration of injections.

To overcome this problem, researchers from Inserm, Institut Pasteur, and the company NEOVACS, have developed a conjugate vaccine, called a kinoid, by coupling the recombinant cytokines IL-4 and IL-13 with a carrier protein called CRM197 (a non-pathogenic mutated form of the diphtheria toxin, used in many conjugate vaccines).

The preclinical results (in animal models) show that this vaccine induces the sustained production of antibodies specifically directed against IL-4 and IL-13. Indeed, six weeks after the first injection of the conjugate vaccine, 90% of the mice presented high levels of antibodies. Over one year after primary immunization, 60% of them still had antibodies capable of neutralizing IL-4 and IL-13 activity.

The researchers also showed an effect on asthma symptoms: the vaccine was able to strongly decrease levels of IgE, eosinophilia, mucus production and airway hyperresponsiveness in a model of dust mite allergic asthma. This study therefore suggests both the prophylactic and therapeutic efficacy of the vaccine in this model of asthma and no adverse effects were observed in the animals.

The research team’s findings will now need to be tested in a clinical trial setting.

Cryotherapy: Very Few Proven Benefits but Very Real Side Effects

©Photo by Scott Rodgerson on Unsplash

In 2010, Inserm and the French Directorate-General of Health signed a partnership agreement to evaluate the health benefits of various forms of alternative medicine practiced in France. In a new report published today, researchers from Inserm focused on cryotherapy, a technique in which the body is exposed for 2 to 3 minutes to intense cold ranging from -110 to -170 °C.

Originally intended for high-level athletes in order to prevent or treat muscle pain after exercise, this practice is now proposed in inflammatory and neurological diseases, and even when there is no disease.

Following analysis of the scientific literature and accounts by experts and patients, the Inserm report concludes that the findings supportive of a positive effect of cryotherapy are modest and had only been measured on a very short term basis.

Furthermore, given the shortcomings in the methodology of the existing studies, the researchers feel that “the positive effects reported must be kept in perspective,” warning that “in any case, cryotherapy can in no way claim to effectively treat cancer or other severe somatic diseases“.

According to the researchers, whole-body cryotherapy also poses genuine safety concerns. Very real side effects have been reported, including burns, headache and chronic cold urticaria. Finally, the report concludes that better quality studies and evaluations of this technique are essential, and that the conditions required to perform these will need to be made possible.

Orthoptic Training and Reduced Screen Exposure: A Winning Combination for Treating Vergence Disorder-Induced Dizziness in Children

boy and girl standing in front of laptop

© stem.T4L on Unsplash

In order to see objects clearly, our eyes need to be able to work together by superimposing the images perceived by each eye: by rotating inwards (convergence) when the object is close, and by releasing this convergence when switching to object farther away. This ability of our eyes to perform symmetrical and coordinated movements (at the same speed and amplitude) is called binocular vergence. Vergence disorders or orthoptic disorders are therefore characterized by poor coordination of the two eyes. In children, these can generate incapacitating symptoms (dizziness, instability, difficulty reading, etc.) which can be responsible for school absenteeism and learning difficulties.

A team of researchers led by Sylvette R. Wiener-Vacher (AP-HP practitioner) and Maria Pia Bucci (CNRS researcher) in Unit 1141 NeuroDiderot: Neurodevelopmental and neurovascular diseases (Inserm/Université de Paris), had previously shown that children presenting with dizziness and normal neurological and vestibular[1] examinations should be screened for vergence disorders. Their latest research, published in Frontiers in Integrative Neuroscience, shows that dizziness linked to vergence disorders in children could be treated by a combination of orthoptic training and reduced screen time.

Over a 3-year period, the research team evaluated the efficacy of orthoptic training in children referred to the ENT Department of Robert-Debré hospital – AP-HP for dizziness. Forty-nine children presenting with vergence insufficiency as sole cause of their symptoms were enrolled in this study, along with 109 healthy control children. Each child was followed up for 9 months and underwent orthoptic evaluation (vergence capacity tests) as well as recordings of the eye movements at various stages of the study: before and 3 months after the start of orthoptic training, and 6 months after the end of the training. The researchers also advised all children to reduce their use of video screens which was intensive (~ 3.6 h per day) and which appeared as a potential aggravating factor. 

In all patients, the dizziness disappeared after the end of the orthoptic training and all eye movement parameters improved significantly.  Six months after the end of the training, this improvement remained stable or continued.

These findings indicate that orthoptic treatment, when combined with instructions to reduce screen time, shows a significant long-term effect on the symptoms of dizziness and on the oculomotor performance of the children being monitored.

“These new findings could have a positive effect on the recognition of the efficacy of orthoptic training, which remains controversial”, specify the authors.

The results of this study also suggest that intensive screen use can aggravate pre-existing latent orthoptic problems, with the researchers specifying that “Today many children are exposed to small video screens for long periods of time. The increasing prevalence of symptomatic vergence insufficiency that we observed could be explained by this lifestyle. ” The authors recommend the inclusion of orthoptic training in clinical tests for children suffering from dizziness as well as reduced exposure to video screens, particularly for children presenting vergence disorders.

[1] The vestibule is part of the inner ear which is involved in maintaining balance.

A Potential New Strategy for Treating Tumors

Coupe transversale d'un mélanome

Coupe transversale d’un mélanome avec les MTA CD163 (macrophages associés aux tumeurs) colorés en vert, les vaisseaux sanguins colorés en rouge et le noyau des cellules coloré en gris. © 2019 Etzerodt et al.

An international team led by Toby Lawrence, Inserm researcher at Unit 1104 Center of Immunology Marseille-Luminy (Inserm / CNRS / Aix-Marseille Université), has developed a potential therapy to reduce tumor size, where previous drugs have failed. Its findings have been published in Journal of Experimental Medicine.

Tumors develop from abnormal cells in the body that continue to grow, forming lumps. While these can be benign, they can also become malignant and lead to cancer.

Malignant tumors, infiltrated by immune cells known as macrophages, usually help the body’s immune defenses. But tumor-associated macrophages (TAMs) are manipulated by cancer cells to not only contribute to the growth and spread of tumors in the body, but also to the suppression of our natural immune defenses against them.

It was in order to counteract this dual mechanism in the growth and spread of tumors that an international team including researchers from Inserm and King’s College London have designed a therapy that targets TAMs without suppressing other macrophages. In a study published in Journal of Experimental Medicine, the researchers explain how they were able to target the “bad” TAMs without suppressing the body’s own natural defenses.

Other recent developments in cancer therapy include drugs known as immune checkpoint inhibitors (ICIs) which have revolutionized the field, especially for melanoma patients. However, patients who do respond to ICI therapy experience severe side effects and over 70% of patients do not respond at all.

In this study, the authors used mouse models of melanoma resistant to ICI therapy.

They were able to specifically target the “bad” TAMs, responsible for massive immune cell recruitment, and significantly reduce tumor size.

According to Toby Lawrence, the Inserm researcher who led the study, this research could lead to the creation of a drug to specifically kill TAMs.

“We were astounded to see how effective targeting a specific subset of TAMs was in reducing tumor growth in this model, where ICI therapy had no impact, he states. This study not only provides a new strategy for targeting specific TAM subsets in the clinic, but also shows why it’s important to target specific TAM subsets and not other macrophages that help anti-tumor immune responses.”

Apparent age of the elderly : a diagnostic tool for primary care physicians?

To estimate the health of their elderly patients, healthcare professionals have various clinical tools at their disposal: geriatric assessment scales, health questionnaires and frailty scores. However, although these tests are appropriate to a medical context, they are more difficult for primary care physicians (PCPs) to implement because they require time and equipment that they do not necessarily possess. When evaluating the general health of an elderly patient, the PCP will first go on their detailed knowledge of him or her as well as the various signs observed during the consultation (physical appearance, gait, etc.).

The objective of the S.AGES cohort[1] was to describe between 2009 and 2014 the medical and paramedical management of patients over the age of 65 using a database generated by PCPs. Practitioners throughout France were enrolled to participate in this study involving the 3-year follow-up of some of their non-institutionalized patients presenting with a satisfactory state of health. In addition to collecting social, demographic and medical data, each PCP was asked to categorize their patients by their apparent age in response to the following question: “In your opinion, does your patient look younger or older than their age or do they look their age? “.

It was on the statistical analysis of the responses to this question that Inserm researchers from the Center for Research in Epidemiology and Population Health focused their attention. The objectives of this study were to analyze the characteristics associated with the PCPs’ estimations and to determine whether these made it possible to predict death within the 3-year follow-up period

The researchers observed that heart problems, depression, obesity, and low levels of autonomy in activities of daily living were primarily linked to patients whose estimated age was higher than their actual age, whereas high levels of education, normal levels of autonomy, lack of depression, lack of vascular problems and chronic hypertension, and low levels of medication were associated with patients who looked younger than their age. Only two variables impacted apparent age in either direction: quality of autonomy and the presence/absence of depression.

Of the patients who died during the 3 years of follow-up: 7.5% belonged to those who looked younger, 8.7% to those who looked their age and 13.8% to those who looked older. It can therefore be taken away from this study that patients who look older present an increased risk of mortality: the age estimation performed by the PCPs is therefore significantly linked to mortality risk.

These results suggest that such age evaluation could be represent a relatively reliable tool in the daily practice of PCPs when estimating the general health of patients. This does not mean replacing the frailty scores but using the practitioner’s clinical sense to support the diagnosis.

[1] The S.AGES cohort was funded by Sanofi and approved by the Ile de France XI ethics committee and the French medicines and health products safety agency

Repurposing Drugs to Fight the Flu: a Phase 2 Clinical Trial for FLUNEXT


The VirPath team from the International Center for Infectiology Research (CIRI, Inserm Unit 1111 – CNRS Joint Research Unit 5308  – ENS Lyon – UCBL1), in collaboration with the laboratory of Dr. Guy Boivin (Canada Research Chair in Emerging Viruses, Infectious Diseases Research Center of the University Hospital of Quebec – Université Laval), has developed and validated an innovative strategy which involves the identification and direct exploitation of clinical samples from infected patients in order to select and use drugs marketed for the treatment of other viruses. A strategy known as “drug repurposing”. This program has been funded by Inserm, the French Directorate of Health Care Supply (DGOS), the French National Research Agency, the Auvergne Rhône-Alpes region, Université Claude Bernard and Université Laval.

This novel and accelerated bedside-to-bench and bench-to-bedside approach is particularly well-suited to acute respiratory infections because it enables the identification and rapid validation of new generations of antivirals which are more effective and treat a broader spectrum of diseases. In addition, the regulatory and financial benefits of this drug repurposing strategy are evident when compared with the long and very costly traditional new-drug development process. The team’s Drug Discovery platform has already demonstrated its potential (three international patents protecting eight repurposed drugs) with the identification of diltiazem (Tildiem®) – usually used in heart pathologies – as an anti-infectious agent in flu viruses.

On the basis of these findings, a phase 2 clinical trial, called FLUNEXT, led by Manuel Rosa-Calatrava, Inserm researcher and Julien Poissy (Inserm Unit 995, Lille Inflammation Research International Center) of Lille University Hospital, began in January 2018. The objective of this national trial is to evaluate the effects of diltiazem in combination with an antiviral, oseltamivir (Tamiflu®), for the treatment of severe flu infections. It intends to enroll 300 patients in ten intensive care units, over two periods of flu epidemic, with final results expected in 2019.

The validation of this strategy and the results already obtained have led to the creation of a startup called Signia Therapeutics. The laboratory’s research program will now be extended to include other respiratory diseases, such as human respiratory syncytial virus and human metapneumovirus, responsible for severe respiratory infections in young children and the elderly.

For more information on the VirPath team and CIRI:

The VirPath website

The CIRI website

What is the Origin of Human Social Intelligence?


In humans, “Theory of Mind” is the ability to understand others’ mental states: what they think, what they feel, what they desire, what they love, etc. It plays a major role in human social interactions.

But where did this ability evolve from? What type of selection pressure ultimately led to this being imparted on the human species?

In order to offer a response, Jean Daunizeau, Inserm Researcher within ICM, Shelly Masi (National Museum of Natural History, MNHN) and her colleagues first developed a means of measuring the level of sophistication of theory of mind, based on behavioral analysis in simple interactive games. After validating this method in humans, they then used it to compare the level of sophistication of theory of mind in seven non-human primate species, from lemurs to the great apes (gorillas, orangutans, and chimpanzees).

Their study is the first to provide data on the origins of human social intelligence. In particular, the results of the study go against the generally accepted hypothesis, which stipulates that theory of mind developed in response to problems arising from the complexity of the social group in which animals evolved.

It appears rather that the evolution of theory of mind was primarily determined by limiting neurobiological factors, such as brain size.

Lastly, the researchers identified a large difference, an evolutionary “gap“, between the capacity of theory of mind in the great apes and humans. This research has been published in PLOS Computational Biology

Drug overconsumption in pregnant women in France


Pregnancy is a sensitive time, particularly in the first months. Pregnant women are therefore strongly advised to limit their use of medicines, as some of their effects are yet poorly known. Nevertheless, a recent study conducted by Inserm researchers from Unit 1181 “Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases”, reveals that pregnant French women are among the largest consumers of drugs worldwide with around ten medicines prescribed during pregnancy. A rate which remained stable throughout the period analyzed (2011-2014).

In the 28,500 women studied, this research reveals that out of the recommended medications, the consumption of antianemia products greatly exceeded the actual prevalence of anemia (72.5% for around 25%). Between 2011 and 2014, the consumption of recommended vitamins (B9 and D) increased by 10% whereas the percentage of women receiving the influenza vaccine increased by only 1%. More worryingly, the exposure to medicines with fetotoxic effects (impairing fetal organ growth and function) and teratogenic effects (causing malformations), while being low, was still too high.

Finally, according to the researchers: “the situation of low-income pregnant women is of additional concern because of their higher average consumption of drug except for recommended vitamins. “

This research was published in Pharmacoepidemiology and Drug Safety.

Benefits of Unit-Dose Antibiotic Sale

Between November 2014 and November 2015, a study conducted by Inserm (Unit 912 SESSTIM – Economic and Social Sciences, Health Systems and Medical Informatics), Université Aix-Marseille, IRD, CNRS and the PACA Regional Health Observatory, trialed the unit-dose dispensing of certain antibiotics across four regions in France. Out of 100 volunteer pharmacies, 75 pharmacies were randomly selected to offer unit-dose dispensing of treatment to patients with a prescription stating one or more of the 14 antibiotics concerned. The results of this trial, published in PLos ONE on September 19, 2017, are as follows:

  • Acceptability of unit-dose dispensing of antibiotics (UDD): 80% of patients with a prescription for an antibiotic treatment concerned by the trial agreed to unit-dose dispensing.
  • Impact on the volumes of medicinal products dispensed: deconditioning was necessary for 60% of patients exposed to unit-dose dispensing. The unit-dose dispensing method reduces the volume of tablets dispensed by approximately 10%, compared to traditional sale.
  • Proper use of treatments: The unit-dose dispensing method prevents the problem of improperly recycled tablets (this is the case for 13% of prescribed antibiotics observed in the study). Lastly, unit-dose dispensing of antibiotics is associated with improved patient adherence to the prescription, according to the measurement of ‘compliance’ based on the number of unused tablets remaining at the end of treatment.

Is Our Stubbornness Caused by Confirmation Bias?

© Fotolia

The way in which people make decisions can sometimes seem reckless or even totally irrational. One explanation for this behavior is that humans tend to prefer information that confirms their beliefs and overlook that which contradicts them. This is a phenomenon called confirmation bias.


In recent research published in PLoS Computational Biology, a team of researchers led by Stefano Palminteri and Sarah-Jayne Blakemore tested 20 subjects by having them choose between two symbols, each worth a different number of points. The aim was to get as many points as possible. The results of this study show that the participants won more points when their choice was followed by feedback. In addition, it was all the more effective when the feedback was positive (“Your choice is the best”) rather than negative (“You would have got more points with a different choice”). This confirmation bias slowed the subjects’ ability to adapt to change to such an extent that it affected the total number of points won by the most biased of the subjects. In conclusion, people preferentially take into account information that confirms rather than contradicts their choices.


According to Stefano Palminteri: “These results may explain why people maintain false beliefs or persist with risky health behaviors, despite obvious information to the contrary. On the other hand, this bias may also enable certain people to maintain motivation and self-esteem.”  Knowing more about the biases in our learning could mean that we learn more effectively and are more aware of our natural inclination to jump to conclusions.