New Whooping Cough Vaccine In Development

Boîte de pétri contenant une Culture de Bordetella pertussis, l’agent causal de la coqueluche.

Culture of Bordetella pertussis, the causative agent of whooping cough ©Inserm/Locht, Camille

A research team from Inserm, Lille University, Lille University Hospital, CNRS, and the Institut Pasteur of Lille, as part of the Lille Immunity and Infection Center, in partnership with ILiAD Biotechnologies, is developing a new vaccine against whooping cough. The researchers are using the whole bacterium, which has been genetically modified to render it nontoxic, in the hopes of compensating for the efficacy failures of the current vaccine. The new vaccine is intended to induce a lasting immune response and block transmission between individuals. New research published in The Lancet Infectious Diseases presents phase 1 results of the clinical trials for this vaccine, which show satisfactory tolerance and an effective response in adults.

Whooping cough is a respiratory illness caused by Bordetella pertussis bacteria. It is highly contagious and can be fatal to infants. Vaccination is recommended for both infants and their families.

The first whooping cough vaccines were developed in the 1950s. These “inactivated” vaccines involved injecting bacteria that had been inactivated by heat or chemical treatments. The vaccines were effective, but they presented the disadvantage of inducing some localized and generalized adverse effects that were bothersome but not serious. A second generation of more easily tolerated vaccines was developed, this time based on the use of just a few bacterial proteins.

These vaccines have been in use in industrialized nations since the 2000s; but in less than ten years it became apparent that whooping cough infection rates in the general population were rising despite vaccination. The current vaccines do indeed provide effective protection from the illness, but their effect lasts only 3 to 5 years and they do not sufficiently block the transmission of bacteria between individuals.

Inserm research director Camille Locht and his team from the Lille Immunity and Infection Center (Inserm/Lille University/Lille University Hospital/CNRS/Institut Pasteur of Lille) together with ILiAD Biotechnologies are working on a new whooping cough vaccine that will be more effective than current vaccines. Like first-generation vaccines, the new vaccine, referred to as BPZE1, relies on whole bacteria but in this case the bacteria are still alive. BPZE1 is, in fact, a “live attenuated” vaccine, meaning that it contains a live infectious agent but whose pathogenic potential is genetically attenuated (rather than having been inactivated by heat).

One of the major challenges of perfecting BPZE1 was finding a way to improve tolerance, which was poor with the first vaccines. After identifying and describing the toxicity genes responsible for the pathological effects of whooping cough, the researchers were able to genetically modify the bacteria to obtain a strain that lacked toxicity, from which BPZE1 was developed. The vaccine is administered via nasal route in the form of an inhalable suspension, which reproduces the natural route of infection and consequently improves the duration of efficacy.

“This vaccine triggers local immunity in the respiratory tract by mobilizing innate immunity, enabling a rapid response,” explains Locht. “Furthermore, the bacteria are quickly eliminated after being introduced into the nasal cavity, which limits transmission. We hope that the effect of BPZE1 will last for at least two decades.”

After satisfactory preclinical trials in animals, the researchers conducted a phase 1 trial in humans to determine whether tolerance was satisfactory and if a response occurred at three different doses of the vaccine with a single nasal administration. The trial was conducted on 48 participants, aged 18 to 32, presenting few antibodies specific to Bordetella pertussis bacteria. They were divided into three groups, one for each of the three doses. In each group, 12 individuals received the vaccine and 4 received a placebo. Nasal and blood samples were taken on six occasions during the first month, then six months later, and, finally, one year later, to check whether the vaccine was present in the mucosa and determine whether a specific immune response had taken place.

The highest dose triggered the production of specific antibodies, which were still present one year later in 100% of the volunteers (the rate was 80% at the lowest dose). Furthermore, all three doses were tolerated well, with adverse effects equivalent to those reported in the placebo groups.

The researchers were encouraged by these results and have begun phase 2 clinical trials in 300 volunteers. “If this vaccine passes all the steps in development, it may be used initially for adults who care for infants, to protect the infants from the possibility of transmission,” Locht specifies. “Use in vulnerable individuals and infants is planned, but this will require additional safety data that it may take a long time to obtain,” he concludes.

Rift Valley Fever: An Example of the Fight Against Emerging Viral Diseases

RVF is transmitted from livestock to humans. © DAAF 976

A viral disease responsible for major epidemics, occurring mainly in Africa, Rift Valley fever (RVF) is transmitted from livestock to humans. Despite being listed as a priority emerging disease by the World Health Organization (WHO) R&D Blueprint program in 2015, there had until now been little research into the dynamics of its transmission. As part of a multidisciplinary collaboration, researchers and public health professionals from Inserm, the French Public Health Agency, Cirad and the London School of Hygiene and Tropical Medicine, with the support of the REACTing consortium, have developed a mathematical model to study the dynamics of the 2018-2019 RVF epidemic in Mayotte and to quantify for the first time the beneficial impact of vaccinating livestock. This research has been published in the journal PNAS.

Against the background of the continued Covid-19 pandemic, research into emerging diseases and zoonoses – infectious diseases transmissible from animals to humans, has never been so important.

Rift Valley fever (RVF) is a viral zoonotic disease occurring primarily in some African regions, Mayotte and the Arabian Peninsula. It mainly affects livestock, causing waves of miscarriage and widespread mortality in the youngest animals. Humans can be infected through direct contact with the body fluids of contaminated animals or through the bites of infected mosquitos. To date, no human-to-human contamination has been reported. While the majority of patients develop asymptomatic or benign forms, in rare cases (1 to 3% of patients) the disease can take a more severe turn, characterized by ocular and meningeal disorders, and life-threatening hemorrhagic fever.

A major public health concern in some countries, RVF was listed by the WHO as an emerging priority disease in 2015, involving the accelerated development of its means of control. While research into vaccines for livestock is making progress, the potential impact of vaccination on the dynamics of the epidemic had never previously been evaluated.

The team, coordinated by Inserm researcher Raphaëlle Métras and her French Public Health Agency colleague Marion Subiros, looked at the 2018-2019 RVF epidemic in Mayotte. Since 2008, thanks to the implementation of two surveillance systems – one concerning the animals (helped by the Veterinary Services of Mayotte), the other humans – a large amount of high-quality RVF surveillance data has been collected. These data concern livestock seroprevalence and human epidemiology (number of human cases, sociodemographic characteristics, disease exposure criteria and geolocation).

As part of their study, the researchers and their colleagues developed a mathematical model integrating these data collected jointly by the two systems in order to reproduce the transmission dynamic of the virus during the 2018-2019 epidemic. One of the objectives was to obtain more information on how the virus passes from infected animals to humans.

What the scientists have shown is that for the first time in the context of an RVF epidemic there was a higher level of transmission to humans from mosquitos than through direct contact with infected livestock. If it is assumed that 30% of the population of Mayotte are farmers, up to 55% of human infections would have been caused by mosquito bites, versus 45% through exposure to livestock.

This is the first study to provide figures on the distribution of transmission through mosquito bites versus transmission through human direct contact.

The team also modeled the potential impact of vaccinating livestock to reduce the scale of the epidemic, using a suitable vaccine with the target characteristics of the WHO Blueprint program (especially vaccine efficacy). The findings of the model show that vaccinating 20% of the livestock could reduce the number of human cases by 30%. Reactive and mass vaccination campaigns in livestock would therefore be an essential measure when it comes to reducing the incidence of the disease in humans.

In a context in which zoonotic disease epidemics are emerging in succession, this research illustrates the importance of implementing a “One Health” approach, taking a systemic and unified approach to public, animal and environmental health at local, national and global levels.“The health emergency associated with the Covid-19 pandemic must force us to rethink how we see the links between human, animal and environmental health. Our research highlights the importance and added value of a multidisciplinary and integrated One Health quantitative approach in fighting zoonotic diseases. They also provide avenues for improving the surveillance of and research into emerging infectious diseases,” concludes Métras.

Early Puberty: Is There a Potential Explanation for Some Cases?

GnRH (red cell) neurons that are born in the nose use olfactory fibers (green and blue marking) to migrate into the brain during fetal life. © European Research Council/Agence Nationale de la Recherche Médicale/Métropole Européenne de Lille

Until now the general consensus had been that puberty was triggered by the acceleration of growth. However, a research team from Inserm, Lille teaching hospital and Université de Lille working at the Lille Neuroscience and Cognition Laboratory has discovered in mice a mechanism associated with the prepubertal growth spurt and the triggering of early puberty. This mechanism is regulated by the GnRH neurons, which orchestrate fertility, through the expression of their protein Nrp1. The team’s findings, published in The EMBO Journal, challenge existing knowledge of the triggers of puberty and pave the way for the study of this mechanism in humans and its potential role in some cases of early puberty.

The general consensus is that a growth spurt at the beginning of puberty triggers the activation of GnRH neurons[1] in the brain and the release of sex hormones. During embryonic development, these GnRH neurons appear in the nose and migrate towards the hypothalamus in the brain – from where they later go on to orchestrate fertility.

This study, conducted by Inserm Research Director Vincent Prévot and his team within the Lille Neuroscience and Cognition laboratory (Inserm/Lille teaching hospital/Université de Lille), has challenged this scientific consensus by re-examining the roles of GnRH neurons in triggering puberty.

This study follows previous research in which Prévot and his team had shown that a protein, called Nrp1, which is present along the axons linking the nose to the olfactory system of the brain, is a component of the “rails” that enable GnRH neurons to migrate from the nose to the brain during embryonic development. However, Nrp1 is also expressed by the GnRH neurons themselves, which led the researchers to study its role in the migration and functioning of those neurons. In order to do that, they developed a mouse model in which Nrp1 was inactivated only in the GnRH neurons but continued to be expressed elsewhere. These neurons were labeled with fluorescence in order to observe them over a period of time.

What the research team observed in the mutated mice was an increase in the quantity of GnRH neurons in the nose, which is associated with migration towards the brain starting earlier. Physiologically, the authors observed weight gain and more rapid growth of the mutated mice in relation to the control animals, as well as an earlier start to puberty.

These observations suggest that the GnRH neurons could in reality control the prepubertal growth spurt and not the other way around as the researchers had hitherto thought.

“We will research connections and communications between the GnRH neurons and the appetite and growth regulation functions to explain this phenomenon, specifies Prévot. It is the first time to my knowledge that these GnRH neurons are attributed functions that differ from reproduction.”

The researchers also saw in the mutated mice that the neurons had colonized an unusual region of the brain, the olfactory bulb – the center of olfactory information processing -, when they are usually only concentrated in the hypothalamus. This observation led them to verify whether the perception of odors – known to play a role in sexual attraction – could be modified. They then observed that very young female mice presenting a lack of Nrp1 had, contrary to those of the control group, a preference for the odors of male mice versus those of members of their own sex. Early puberty in those mutated mice could therefore be accompanied by sexual attraction that also takes place earlier.

It remains to be verified whether these mechanisms occur in humans. “These findings suggest that a very early growth spurt could be associated with early GnRH neuron activation. A phenomenon that could also be associated with certain variants of the NRP1 gene. These results open up new avenues in preventing the risks of early puberty in children. We will now go on to explore the inhibition of GnRH neural activity with drugs that are already used in a clinical setting”, envisages Prévot.


[1] A group of cells in the hypothalamus secrete gonadotropin-releasing hormone (GnRH),  which controls puberty and fertility. GnRH stimulates secretion of the sex hormones LH and FSH that in turn stimulate the gonads. Acquiring these functions is a lengthy process that starts with the migration of the GnRH cells in the nose towards the brain during embryonic development, and then continues with their maturation and activation at puberty.

Consumption of Foods With Lower Nutri-Scores Associated With Higher Mortality

New study looks at the link between nutritional quality of foods and mortality. © Adobe Stock

Consuming food products that rank lower on the nutritional quality score underlying the Nutri-Score logo is associated with higher mortality, according to the European cohort EPIC. These findings, obtained by researchers from Inserm, Inrae, Cnam and Université Sorbonne Paris Nord, in collaboration with researchers from the International Agency for Research on Cancer (WHO/IARC), confirm the relevance of Nutri-Score in the context of public health policy. The study was published on September 17, 2020 in the British Medical Journal (BMJ).

While it is now well established that a diet lower in sugars, saturated fats, salt and energy and higher in fiber, fruit and vegetables is better for health – helping to prevent the risk of chronic conditions, such as cancer or cardiovascular diseases – putting these recommendations into practice remains a major challenge.

With this in mind, the Nutri-Score logo was developed to help consumers choose foods with a better nutritional quality at the point of purchase and to incentivize manufacturers to improve the nutritional quality of their products. Nutri-Score is a front-of-pack label that uses 5 colors and provides information on the nutritional quality of food products: from category A (dark green) indicating higher nutritional quality to category E (dark orange) indicating lower nutritional quality. The colors used by Nutri-Score are attributed on the basis of Food Standards Agency nutrient profiling system, modified version (FSAm-NPS) scores, which reflect the nutritional profile of foods according to their content (per 100 g) in terms of energy, sugars, saturated fatty acids, sodium, protein, fiber and fruit and vegetables.

A number of studies published in international scientific journals have shown the validity of the FSAm-NPS score in characterizing the nutritional quality of food products as well as the efficacy of Nutri-Score in guiding consumers towards more nutritious choices. In particular, links between the consumption of foods whose FSAm-NPS scores indicate higher nutritional quality (reflected in higher Nutri-Scores) and better health have so far been observed in France (SU.VI.MAX and NutriNet-Santé cohorts), the United Kingdom (Whitehall II and EPIC-Norfolk cohorts) and Spain (SUN cohort).

The aim of the new study published in the BMJ and conducted by the Nutritional Epidemiology Research Team (EREN) at the Epidemiology and Statistics Research Center – Université de Paris (Inserm/Inrae/Cnam/Université Sorbonne Paris Nord) was to look for links between the FSAm-NPS scores of the foods consumed and mortality within a very broad population distributed across 10 European countries. It follows on from a study published in 2018, which was conducted in the same population in relation to cancer risk.

In total, 501,594 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were included in the analyses. During the 1992 to 2015 follow-up period, 53,112 participants died of non-accidental causes (including cancer and diseases of the circulatory, respiratory and digestive systems).

The researchers show that those participants who consumed on average more foods with FSAm-NPS scores indicating lower nutritional quality (reflected in lower Nutri-Scores), presented higher mortality (total mortality and mortality linked to cancer and diseases of the circulatory, respiratory and digestive systems).

Findings which were statistically significant once a large number of sociodemographic and lifestyle characteristics were taken into account.

Nutri-Score was officially adopted in France in 2017 and since then by various other European countries (Belgium, Spain, Germany, Netherlands, Switzerland and Luxembourg). Nevertheless, under current European labeling regulations the inclusion of this logo is optional and as such depends on the willingness of the food manufacturers. Although over 350 companies and brands so far have undertaken to include Nutri-Score on their products, one crucial point remains the necessity, in the near future, for Europe-wide harmonization making it mandatory to implement an effective and useful logo for consumers. This harmonization is envisaged for the year 2022 as part of the Farm to Fork strategy presented in May by the European Commission.

“In this context, our findings, combined with the various other findings available on the subject, help to show not just the capacity of FSAm-NPS and Nutri-Score to characterize the nutritional quality of foods but also the relevance of their use in the context of public health policies aimed at guiding consumers towards healthier food choices in order to prevent chronic diseases,” emphasize Inserm researchers Mélanie Deschasaux and Mathilde Touvier, who coordinated the study.

Research shows that treatment with growth hormone in children who have recovered from cancer does not increase the risk of a second tumor.

Growth hormone deficiency is a common complication of radiotherapy. © Adobe Stock


Teams from Bicêtre AP-HP hospital, Inserm, Gustave Roussy and the University of Paris-Saclay studied the influence of growth hormone treatment on the risk of a second tumor. in 2,852 adults recovered from childhood cancer. The data confirm that treatment with growth hormone in these children with growth hormone deficiency does not increase the risk of developing a second cancer. This study therefore provides reassuring data on the long-term fate of these children cured of cancer and treated with growth hormone to enable them to reach normal adult height. The results of this study were published in the European Journal of Endocrinology in September 2020.

Growth hormone deficiency is a common complication of brain radiation therapy. Children treated with radiation therapy need growth hormone treatment to reach normal adult height, but there have been concerns about a possible increased risk of another tumor developing in adulthood caused by it. growth hormone treatment.

Researchers from unit 1018 of the “Center for Research in Epidemiology and Population Health (CESP)” (Inserm / Université Paris-Saclay / Gustave Roussy) and from Bicêtre AP-HP hospital, analyzed data from a French cohort, Euro2k, which brings together 2,852 survivors of pediatric cancer diagnosed before the age of 18 before 1986. Among them, 196 had been treated in childhood with growth hormone.

The research team studied the influence of growth hormone treatment on the occurrence of second tumors with a follow-up of 26 years, taking into account the doses of radiation received by all the organs of the body. These were obtained by reconstituting the radiotherapy received for each child. 

In this cohort, 374 survivors developed a second tumor, 40 of whom received growth hormone treatment in childhood. Analysis of the data shows that treatment with growth hormone is not associated with an increased risk of second tumors. However, these researchers found in survivors who received growth hormone treatment for more than 4 years, a slight increase (x2) risk of meningioma, a benign tumor of the meninges favored by high doses of radiotherapy. This slight excess risk of meningioma in survivors who received more than 4 years of treatment with growth hormone is not significant, however, and there is no evidence that the treatment with growth hormone either. responsible.

“This study provides information on the long-term fate of the children whom we treat with growth hormone for a growth hormone deficiency secondary to the treatment of their cancer. These new data allow us to approach the treatment with growth hormone calmly. in these children cured of cancer, when necessary and to reassure families about the absence of an increased risk of second tumors during this treatment. concludes Dr Cécile Thomas-Teinturier, pediatrician-endocrinologist at the Bicêtre AP-HP hospital and first author of the study.

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