title: Non-invasive epicutaneous vaccine against Respiratory Syncytial Virus: Preclinical proof of concept.
abstract: 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. Such a needle-free vaccine may have a better acceptability for the vaccination of sensible population such as infants since it does not require any skin preparation. Moreover, this self-applicative vaccine would overcome some issues associated to injectable vaccines such as the requirement of sterile medical devices, the need of skilled health-care professionals and the necessity of stringent store conditions. Here, we demonstrate that Viaskin® patches loaded with a formulation containing N-nanorings (Viaskin®-N) are highly immunogenic in mice and promotes a Th1/Th17 oriented immune response. More importantly, Viaskin®-N epicutaneous vaccine confers a high level of protection against viral replication upon RSV challenge in mice, without exacerbating clinical symptoms. In swine, which provides the best experimental model for the transcutaneous passage of drug/antigen in human skin, we have shown that GFP fluorescent N-nanorings, delivered epicutaneously with Viaskin® patches, are taken up by epidermal Langerhans cells. We have also demonstrated that Viaskin®-N induced a significant RSV N-specific T-cell response in pig. In conclusion, Viaskin®-N epicutaneous vaccine seems efficient to protect against RSV infection in animal model.
authors.affiliation: DBV Technologies, 177-181 avenue Pierre Brossolette, 92120 Montrouge, France. Electronic address: pierre-louis.herve@dbv-technologies.com.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Hervé
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Delphyne
authors.initials: D
authors.lastname: Descamps
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Deloizy
authors.affiliation: DBV Technologies, 177-181 avenue Pierre Brossolette, 92120 Montrouge, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Dhelft
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Daphné
authors.initials: D
authors.lastname: Laubreton
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Edwige
authors.initials: E
authors.lastname: Bouguyon
authors.affiliation: GABI, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Abdelhak
authors.initials: A
authors.lastname: Boukadiri
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubuquoy
authors.affiliation: APEX, INRA, Rue de la Geraudière, 44000 Nantes, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Larcher
authors.affiliation: DBV Technologies, 177-181 avenue Pierre Brossolette, 92120 Montrouge, France.
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Benhamou
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eléouët
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bertho
authors.affiliation: DBV Technologies, 177-181 avenue Pierre Brossolette, 92120 Montrouge, France. Electronic address: lucie.mondoulet@dbv-technologies.com.
authors.forename: Lucie
authors.initials: L
authors.lastname: Mondoulet
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France. Electronic address: sabine.riffault@jouy.inra.fr.
authors.forename: Sabine
authors.initials: S
authors.lastname: Riffault
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D005260:Female; D007801:Langerhans Cells / Q000378:metabolism; D051379:Mice; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D012869:Skin Absorption; D013045:Species Specificity; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*; D057968:Transdermal Patch; D014779:Virus Replication / Q000276:immunology*
chemical_list: D022261:Respiratory Syncytial Virus Vaccines
keywords: Cutaneous vaccine; N-nanoring nanoparticle; Respiratory Syncytial Virus; Viaskin® patch