Epicutaneous immunization using synthetic virus-like particles efficiently boosts protective immunity to respiratory syncytial virus.

Despite the substantial health and economic burden caused by RSV-associated illness, no vaccine is available. The sole licensed treatment (palivizumab), composed of a monoclonal neutralizing antibody, blocks the fusion of the virus to the host cell but does not prevent infection. The development of a safe and efficacious RSV vaccine is therefore a priority, but also a considerable challenge, and new innovative strategies are warranted.

Epicutaneous Tolerance Induction to a Bystander Antigen Abrogates Colitis and Ileitis in Mice.

Background: Although inflammatory bowel disease (IBD) is a failure in maintaining tolerance to the intestinal microbiota, few studies have investigated the use of immunologic tolerance as a treatment approach for IBD. We hypothesized that induction of immune tolerance at a distal site could suppress intestinal inflammation through a process of bystander regulation.

Methods: Epicutaneous tolerance was induced by topical application of ovalbumin (OVA) using a Viaskin patch for 48 hours.

Non-invasive epicutaneous vaccine against Respiratory Syncytial Virus: Preclinical proof of concept.

To put a Respiratory Syncytial Virus (RSV) vaccine onto the market, new vaccination strategies combining scientific and technical innovations need to be explored. Such a vaccine would also need to be adapted to the vaccination of young children that are the principal victims of acute RSV infection. In the present project, we describe the development and the preclinical evaluation of an original epicutaneous RSV vaccine that combines two technologies: Viaskin® epicutaneous patches as a delivery platform and RSV N-nanorings (N) as a subunit antigen.

Epicutaneous immunotherapy induces gastrointestinal LAP regulatory T cells and prevents food-induced anaphylaxis.

Background: The attempt to induce oral tolerance as a treatment for food allergy has been hampered by a lack of sustained clinical protection. Immunotherapy by nonoral routes, such as the skin, may be more effective for the development of maintained tolerance to food allergens.

Objective: We sought to determine the efficacy and mechanism of tolerance induced by epicutaneous immunotherapy (EPIT) in a model of food-induced anaphylaxis.

Differences in phenotype, homing properties and suppressive activities of regulatory T cells induced by epicutaneous, oral or sublingual immunotherapy in mice sensitized to peanut.

Allergen-specific immunotherapy has been proposed as an attractive strategy to actively treat food allergy using the following three different immunotherapy routes: oral (OIT), sublingual (SLIT) and epicutaneous (EPIT) immunotherapy. Regulatory T cells (Tregs) have been shown to have a pivotal role in the mechanisms of immunotherapy. The aim of this study was to compare the phenotype and function of Tregs induced in peanut-sensitized BALB/c mice using these three routes of treatment.

Epicutaneous immunotherapy for food allergy as a novel pathway for oral tolerance induction.

Epicutaneous immunotherapy is a developing technique, aiming at desensitizing patients with food allergy with less risks that oral ingestion or injection could generate. Several clinical trials have been performed and are currently running, in milk and peanut allergy, assessing the safety of the technique and its efficacy. Preclinical models indicate a major role in the mechanisms of desensitization, for example, Tregs and epigenetic modifications.

Needle-free and adjuvant-free epicutaneous boosting of pertussis immunity: Preclinical proof of concept.

The limited durability of pertussis vaccine-induced protection requires novel approaches to reactivate immunity and limit pertussis resurgence in older children and adults. We propose that periodic boosters could be delivered using a novel epicutaneous delivery system (Viaskin) to deliver optimized pertussis antigens such as genetically-detoxified pertussis toxin (rPT). To best mimic the human situation in which vaccine-induced memory cells persist, whereas antibodies wane, we developed a novel adoptive transfer murine model of pertussis immunity.

Specific epicutaneous immunotherapy prevents sensitization to new allergens in a murine model.

Background: Allergy to cow's milk increases the risk of sensitization to other foods in young children.

Objectives: We sought to evaluate the effect of early epicutaneous immunotherapy (EPIT) on further sensitization to peanut or house dust mite (HDM) in a murine model of sensitization to cow's milk.

Methods: BALB/c mice orally sensitized to milk were epicutaneously treated with a Viaskin patch (DBV Technologies) loaded with milk proteins for 8 weeks.

Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT) in mice.

Background: Epicutaneous immunotherapy (EPIT) on intact skin with an epicutaneous delivery system has already been used in preclinical and clinical studies. In epicutaneous vaccination and immunotherapy, the stripping of skin before application of the allergen is suggested to facilitate the passage of allergen through immune cells.

Objectives: The aim of this study was to compare the immunological response induced by EPIT performed on intact and stripped skin in a mouse model of peanut allergy.

Epicutaneous immunotherapy (EPIT) blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice.

Background: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice.

Epicutaneous Immunotherapy Compared with Sublingual Immunotherapy in Mice Sensitized to Pollen (Phleum pratense).

Background. The aim of this study was to compare the efficacy of epicutaneous immunotherapy (EPIT) to sublingual immunotherapy (SLIT) in a model of mice sensitized to Phleum pratense pollen. Methods.

Epicutaneous immunotherapy results in rapid allergen uptake by dendritic cells through intact skin and downregulates the allergen-specific response in sensitized mice.

Epicutaneous immunotherapy onto intact skin has proved to be an efficient and safe alternative treatment of allergy in an animal model with various allergens and in children for cow's milk allergy. The aim of this study was to analyze the different steps of the immunological handling of the allergen when deposited on intact skin using an epicutaneous delivery system and its immune consequences in sensitized BALB/c mice. As expected, when applied on intact skin, OVA exhibits neither a passive passage through the skin nor any detectable systemic delivery.

Epicutaneous immunotherapy using a new epicutaneous delivery system in mice sensitized to peanuts.

Background: Peanut allergy is a life-threatening condition for which new efficient and safe treatment is expected. We evaluated epicutaneous immunotherapy (EPIT) as a new alternative treatment for peanut allergy in sensitized mice.

Methods: Sixty BALB/c mice were sensitized by gavages with peanut protein extract (PPE) mixed with cholera toxin.

A dose determination study of polyethylene glycol 4000 in constipated children: factors influencing the maintenance dose.

Objectives: To determine the doses of polyethylene glycol (PEG) 4000 without additional salts allowing normal bowel habits in childhood functional constipation.

Methods: This multicenter noncomparative study allocated children to 4 groups: 6-12 months, 13 months-3 years, 4-7 years, and 8-15 years. Constipation was defined as <1 stool/d for more than 1 month in children aged 6-12 months and <3 stools/w for more than 3 months in older children.

Digestive endoscopy in neonates.

Since the introduction of flexible fiberoptic endoscopy in the early 1970s, esophagogastro-duodenoscopy and colonoscopy have become established procedures for the diagnosis, evaluation and treatment of gastrointestinal tract disease in the pediatric population. The development of safe fiberoptic endoscopes specially designed for neonates has allowed visualization of lesions occurring in the first days of life. Despite an increased understanding of neonatal digestive disorders deriving from this new diagnostic modality, there is little consensus on the appropriate use of endoscopic procedures in routine care of neonates.

Correlation between gastric acid secretion and severity of acid reflux in children.

The purpose of our study was to systematically evaluate gastric acid output in children with long-lasting gastro-esophageal reflux (GER) in order to assess its mechanism and the need for anti-acid treatment. The investigation was carried out in 20 males and 10 females, aged 7.5 +/- 3.