title: Intradermal vaccination with un-adjuvanted sub-unit vaccines triggers skin innate immunity and confers protective respiratory immunity in domestic swine.
abstract: Intradermal (ID) vaccination constitutes a promising approach to induce anti-infectious immunity. This route of immunization has mostly been studied with influenza split-virion vaccines. However, the efficacy of ID vaccination for sub-unit vaccines in relation to underlying skin innate immunity remains to be explored for wider application in humans. Relevant animal models that more closely mimic human skin immunity than the widely used mouse models are therefore necessary. Here, we show in domestic swine, which shares striking anatomic and functional properties with human skin, that a single ID delivery of pseudorabies virus (PRV) glycoproteins without added adjuvant is sufficient to trigger adaptive cellular and humoral immune responses, and to confer protection from a lethal respiratory infection with PRV. Analysis of early events at the skin injection site revealed up-regulation of pro-inflammatory cytokine and chemokine genes, recruitment of neutrophils and monocytes and accumulation of inflammatory DC. We further show that the sustained induction of pro-inflammatory cytokine genes results from the combined effects of skin puncture, liquid injection in the dermis and viral antigens. These data highlight that immune protection against respiratory infection can be induced by ID vaccination with a subunit vaccine and reveal that adjuvant requirements are circumvented by the mechanical and antigenic stress caused by ID injection, which triggers innate immunity and mobilization of inflammatory DC at the immunization site. ID vaccination with sub-unit vaccines may thus represent a safe and efficient solution for protection against respiratory infections in swine and possibly also in humans, given the similarity of skin structure and function in both species.
authors.affiliation: CIRI, International Center for Infectiology Research, "Mucosal immunity, Vaccination & Biotherapies" Team, Université de Lyon, Lyon, France; Inserm, U1111, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France; CNRS, UMR 5308, Lyon, France.
authors.forename: Jean-Benoît
authors.initials: JB
authors.lastname: Le Luduec
authors.affiliation: CIRI, International Center for Infectiology Research, "Mucosal immunity, Vaccination & Biotherapies" Team, Université de Lyon, Lyon, France; Inserm, U1111, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France; CNRS, UMR 5308, Lyon, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Debeer
authors.affiliation: Sanofi Pasteur, 1541 avenue Marcel Mérieux, 69280 Marcy L'Etoile, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Piras
authors.affiliation: Merial S.A.S., Laboratoire Lyon Gerland, 254 rue Marcel Mérieux, 69007 Lyon, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Andréoni
authors.affiliation: Sanofi Pasteur, 1541 avenue Marcel Mérieux, 69280 Marcy L'Etoile, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Boudet
authors.affiliation: BD Medical-Pharmaceutical Systems, 11, rue Aristide Bergès, 38800 Le Pont de Claix, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Laurent
authors.affiliation: CIRI, International Center for Infectiology Research, "Mucosal immunity, Vaccination & Biotherapies" Team, Université de Lyon, Lyon, France; Inserm, U1111, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France; CNRS, UMR 5308, Lyon, France. Electronic address: dominique.kaiserlian@inserm.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Kaiserlian
authors.affiliation: CIRI, International Center for Infectiology Research, "Mucosal immunity, Vaccination & Biotherapies" Team, Université de Lyon, Lyon, France; Inserm, U1111, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France; CNRS, UMR 5308, Lyon, France. Electronic address: bertrand.dubois@lyon.unicancer.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dubois
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007113:Immunity, Innate; D007271:Injections, Intradermal; D011557:Pseudorabies / Q000517:prevention & control*; D012867:Skin / Q000276:immunology*; D013552:Swine; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C042966:pseudorabies virus glycoproteins
keywords: Anti-viral immunity; Dendritic cells; Intradermal vaccination; Monocytes; Swine