Targeting human langerin promotes HIV-1 specific humoral immune responses.

Autor: Kervevan J; Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France., Bouteau A; Baylor Institute for Immunology Research (BIIR), Vaccine Research Institute, Dallas, Texas, United States of America.; Institute of Biomedical Studies, Baylor University, Waco, Texas, United States of America.; Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, Pennsylvania, United States of America., Lanza JS; Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS, Marseille, France.; Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France., Hammoudi A; Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France., Zurawski S; Baylor Institute for Immunology Research (BIIR), Vaccine Research Institute, Dallas, Texas, United States of America., Surenaud M; Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France., Dieudonné L; Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France., Bonnet M; College of Biomedical and Life Sciences, University of Cardiff, Cardiff, United Kingdom., Lefebvre C; Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France., Hocini H; Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France., Marlin R; CEA, Université Paris-Sud, Inserm, U1184 'Immunology of Viral Infections and Autoimmune Diseases' (IMVA), IDMIT Department, IBFJ, Fontenay-aux-Roses, France., Guguin A; Inserm U955 -Plateforme de Cytométrie, Institut Mondor de Recherche Biomédicale, UPEC, Créteil, France., Hersant B; Department of plastic and maxillo-facial surgery, Henri Mondor Hospital, Créteil, France., Hermeziu O; Department of plastic and maxillo-facial surgery, Henri Mondor Hospital, Créteil, France., Menu E; CEA, Université Paris-Sud, Inserm, U1184 'Immunology of Viral Infections and Autoimmune Diseases' (IMVA), IDMIT Department, IBFJ, Fontenay-aux-Roses, France.; MISTIC Group, Department of Virology, Institut Pasteur, Paris, France., Lacabaratz C; Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France., Lelièvre JD; Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France., Zurawski G; Baylor Institute for Immunology Research (BIIR), Vaccine Research Institute, Dallas, Texas, United States of America., Godot V; Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France., Henri S; Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France., Igyártó BZ; Baylor Institute for Immunology Research (BIIR), Vaccine Research Institute, Dallas, Texas, United States of America.; Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, Pennsylvania, United States of America., Levy Y; Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France.; AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses, Créteil, France., Cardinaud S; Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2021 Jul 29; Vol. 17 (7), pp. e1009749. Date of Electronic Publication: 2021 Jul 29 (Print Publication: 2021).
DOI: 10.1371/journal.ppat.1009749
Abstrakt: The main avenue for the development of an HIV-1 vaccine remains the induction of protective antibodies. A rationale approach is to target antigen to specific receptors on dendritic cells (DC) via fused monoclonal antibodies (mAb). In mouse and non-human primate models, targeting of skin Langerhans cells (LC) with anti-Langerin mAbs fused with HIV-1 Gag antigen drives antigen-specific humoral responses. The development of these immunization strategies in humans requires a better understanding of early immune events driven by human LC. We therefore produced anti-Langerin mAbs fused with the HIV-1 gp140z Envelope (αLC.Env). First, we show that primary skin human LC and in vitro differentiated LC induce differentiation and expansion of naïve CD4+ T cells into T follicular helper (Tfh) cells. Second, when human LC are pre-treated with αLC.Env, differentiated Tfh cells significantly promote the production of specific IgG by B cells. Strikingly, HIV-Env-specific Ig are secreted by HIV-specific memory B cells. Consistently, we found that receptors and cytokines involved in Tfh differentiation and B cell functions are upregulated by LC during their maturation and after targeting Langerin. Finally, we show that subcutaneous immunization of mice by αLC.Env induces germinal center (GC) reaction in draining lymph nodes with higher numbers of Tfh cells, Env-specific B cells, as well as specific IgG serum levels compared to mice immunized with the non-targeting Env antigen. Altogether, we provide evidence that human LC properly targeted may be licensed to efficiently induce Tfh cell and B cell responses in GC.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: GZ, SZ, and YL are named inventors on patent applications held by Inserm and BIIR concerning Langerin targeting. All other authors have declared that no competing interest exist.
Databáze: MEDLINE
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