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.

Pre-Existing Humoral Immunity Enhances Epicutaneously-Administered Allergen Capture by Skin DC and Their Migration to Local Lymph Nodes.

Due to its richness in antigen presenting cells, e.g., dendritic cells (DC), the skin has been identified as a promising route for immunotherapy and vaccination.

Epidermal micro-perforation potentiates the efficacy of epicutaneous vaccination.

The skin is an immune organ comprised of a large network of antigen-presenting cells such as dendritic cells, making it an attractive target for the development of new vaccines and immunotherapies. Recently, we developed a new innovative and non-invasive vaccination method without adjuvant based on epicutaneous vaccine patches on which antigen forms a dry deposit. Here we describe in mice a method for potentiating the efficacy of our epicutaneous vaccination approach using a minimally invasive and epidermis-limited skin preparation based on laser-induced micro-perforation.

Antigen Uptake by Langerhans Cells Is Required for the Induction of Regulatory T Cells and the Acquisition of Tolerance During Epicutaneous Immunotherapy in OVA-Sensitized Mice.

The skin is a major immunologic organ that may induce protection, sensitization or tolerance. Epicutaneous immunotherapy (EPIT) has been proposed as an attractive strategy to actively treat food allergy and has been shown to induce tolerance in sensitized mice through the induction of Foxp3 regulatory T cells (Tregs), especially CD62L Tregs. Among immune cells in the skin, dendritic cells are key players in antigen-specific immune activation or regulation.

Gata3 hypermethylation and Foxp3 hypomethylation are associated with sustained protection and bystander effect following epicutaneous immunotherapy in peanut-sensitized mice.

Background: Epicutaneous immunotherapy (EPIT) is a promising method for treating food allergies. In animal models, EPIT induces sustained unresponsiveness and prevents further sensitization mediated by Tregs. Here, we elucidate the mechanisms underlying the therapeutic effect of EPIT, by characterizing the kinetics of DNA methylation changes in sorted cells from spleen and blood and by evaluating its persistence and bystander effect compared to oral immunotherapy (OIT).

Treatment of gastric eosinophilia by epicutaneous immunotherapy in piglets sensitized to peanuts.

Background: Eosinophilic gastrointestinal disorders (EGIDs) are hypersensitivity disorders frequently triggered by food allergy and manifested by mucosal eosinophilic infiltration at any level of the gastrointestinal tract. This study established a model of gastric eosinophilia in peanut-sensitized piglets to evaluate the efficacy of epicutaneous immunotherapy (EPIT) for its treatment.

Methods: Experiments were carried out in piglets first sensitized by three intra-peritoneal injections of peanut protein extract (PPE) with adjuvant, and then given PPE orally for 10 days, a sequence leading to gastric eosinophilia assessed by endoscopy.

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.

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.

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.

The regulatory T cells induction by epicutaneous immunotherapy is sustained and mediates long-term protection from eosinophilic disorders in peanut-sensitized mice.

Background: Allergen-specific immunotherapy favours immune deviation from a Th2 to a Th1 response and increases the number of regulatory T cells (Tregs). Epicutaneous immunotherapy (EPIT) of sensitized mice decreases the clinical and the allergen-specific Th2 responses and increases local and peripheral Foxp3(+) Tregs.

Objective: To investigate the role of Tregs in EPIT and characterize their phenotype and maintenance following EPIT.

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 on intact skin using a new delivery system in a murine model of allergy.

Background: Allergen-specific immunotherapy, subcutaneous immunotherapy (SCIT) or oral, has been used for almost a century to redirect inappropriate immune responses in atopic patients. A new mode of administration through the intact skin [epicutaneous immunotherapy (EPIT)], using an original epicutaneous delivery system, may represent an alternative to these classical methods.

Objective: Proof of concept of efficacy of EPIT on intact skin in mice sensitized to aeroallergens or food allergens.