title: Intradermal injection of an anti-Langerin-HIVGag fusion vaccine targets epidermal Langerhans cells in nonhuman primates and can be tracked in vivo.
abstract: The development of new immunization strategies requires a better understanding of early molecular and cellular events occurring at the site of injection. The skin is particularly rich in immune cells and represents an attractive site for vaccine administration. Here, we specifically targeted vaccine antigens to epidermal Langerhans cells (LCs) using a fusion protein composed of HIV antigens and a monoclonal antibody targeting Langerin. We developed a fluorescence imaging approach to visualize, in vivo, the vaccine-targeted cells. Studies were performed in nonhuman primates (NHPs) because of their relevance as a model to assess human vaccines. We directly demonstrated that in NHPs, intradermally injected anti-Langerin-HIVGag specifically targets epidermal LCs and induces rapid changes in the LC network, including LC activation and migration out of the epidermis. Vaccine targeting of LCs significantly improved anti-HIV immune response without requirement of an adjuvant. Although the co-injection of the TLR-7/8 synthetic ligand, R-848 (resiquimod), with the vaccine, did not enhance significantly the antibody response, it stimulated recruitment of HLA-DR+ inflammatory cells to the site of immunization. This study allowed us to characterize the dynamics of early local events following the injection of a vaccine-targeted epidermal LCs and R-848.
authors.affiliation: Université Paris-Sud, UMR 1184, 94276 Le Kremlin Bicêtre, France.|CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT Center, France.|Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, France.|Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Nina
authors.initials: N
authors.lastname: Salabert
authors.affiliation: Université Paris-Sud, UMR 1184, 94276 Le Kremlin Bicêtre, France.|CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT Center, France.|Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, France.|Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Biliana
authors.initials: B
authors.lastname: Todorova
authors.affiliation: Université Paris-Sud, UMR 1184, 94276 Le Kremlin Bicêtre, France.|CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT Center, France.|Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, France.|Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Martinon
authors.affiliation: CEA, Institute of Biomedical Imaging (I2BM), DSV/I2BM/SHFJ/INSERM U1023, CEA, Orsay, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Boisgard
authors.affiliation: Vaccine Research Institute (VRI), Créteil, France.|Baylor Institute for Immunology Research, Dallas, TX, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.affiliation: Vaccine Research Institute (VRI), Créteil, France.|Baylor Institute for Immunology Research, Dallas, TX, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zurawski
authors.affiliation: Université Paris-Sud, UMR 1184, 94276 Le Kremlin Bicêtre, France.|CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT Center, France.|Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, France.|Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.affiliation: Université Paris-Sud, UMR 1184, 94276 Le Kremlin Bicêtre, France.|CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT Center, France.|Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, France.|Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cosma
authors.affiliation: CEA, Photonic Microscopy Platform, Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), DSV, Fontenay aux Roses, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Kortulewski
authors.affiliation: Vaccine Research Institute (VRI), Créteil, France.|Baylor Institute for Immunology Research, Dallas, TX, USA.
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.affiliation: Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.affiliation: Université Paris-Sud, UMR 1184, 94276 Le Kremlin Bicêtre, France.|CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT Center, France.|Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, France.|Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.affiliation: Université Paris-Sud, UMR 1184, 94276 Le Kremlin Bicêtre, France.|CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT Center, France.|Inserm, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, France.|Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chapon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000097:blood; D015703:Antigens, CD / Q000008:administration & dosage / Q000276:immunology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D016655:HIV Core Protein p24 / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000276:immunology; D007271:Injections, Intradermal; D000069416:Intravital Microscopy; D007801:Langerhans Cells / Q000276:immunology* / Q000648:ultrastructure; D037181:Lectins, C-Type / Q000008:administration & dosage / Q000276:immunology*; D008252:Macaca fascicularis; D037241:Mannose-Binding Lectins / Q000008:administration & dosage / Q000276:immunology*; D061848:Optical Imaging; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015703:Antigens, CD; C121916:CD207 protein, human; D016655:HIV Core Protein p24; D007093:Imidazoles; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D014612:Vaccines; C402365:resiquimod
keywords: Fluorescence imaging; Langerhans cell; Nonhuman primate; Skin; Vaccination