Authors
Jérôme Kervevan, Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France
Aurélie Bouteau, 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 AmericaFollow
Juliane S Lanza, Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS, Marseille, France; Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France
Adele Hammoudi, Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France
Sandra Zurawski, Baylor Institute for Immunology Research (BIIR), Vaccine Research Institute, Dallas, Texas, United States of America
Mathieu Surenaud, Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France
Lydie Dieudonné, Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France
Marion Bonnet, College of Biomedical and Life Sciences, University of Cardiff, Cardiff, United Kingdom
Cécile Lefebvre, Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France
Hakim Hocini, Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France
Romain Marlin, CEA, Université Paris-Sud, Inserm, U1184 "Immunology of Viral Infections and Autoimmune Diseases" (IMVA), IDMIT Department, IBFJ, Fontenay-aux-Roses, France
Aurélie Guguin, Inserm U955 -Plateforme de Cytométrie, Institut Mondor de Recherche Biomédicale, UPEC, Créteil, France
Barbara Hersant, Department of plastic and maxillo-facial surgery, Henri Mondor Hospital, Créteil, France
Oana Hermeziu, Department of plastic and maxillo-facial surgery, Henri Mondor Hospital, Créteil, France
Elisabeth Menu, 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
Christine Lacabaratz, Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France
Jean-Daniel Lelièvre, Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France
Gerard Zurawski, Baylor Institute for Immunology Research (BIIR), Vaccine Research Institute, Dallas, Texas, United States of America
Véronique Godot, Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France
Sandrine Henri, Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France
Botond Z. Igyártó, 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 AmericaFollow
Yves Levy, 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
Sylvain Cardinaud, Vaccine Research Institute, Créteil, France, Inserm U955, Équipe 16, Créteil, France
Publication Date
7-29-2021
Abstract
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.
Recommended Citation
Kervevan, Jérôme; Bouteau, Aurélie; Lanza, Juliane S; Hammoudi, Adele; Zurawski, Sandra; Surenaud, Mathieu; Dieudonné, Lydie; Bonnet, Marion; Lefebvre, Cécile; Hocini, Hakim; Marlin, Romain; Guguin, Aurélie; Hersant, Barbara; Hermeziu, Oana; Menu, Elisabeth; Lacabaratz, Christine; Lelièvre, Jean-Daniel; Zurawski, Gerard; Godot, Véronique; Henri, Sandrine; Igyártó, Botond Z.; Levy, Yves; and Cardinaud, Sylvain, "Targeting human langerin promotes HIV-1 specific humoral immune responses." (2021). Department of Microbiology and Immunology Faculty Papers. Paper 129.
https://jdc.jefferson.edu/mifp/129
Comments
This article is the author's final published version in PLoS Pathogens, Volume 17, Issue 7, July 2021, Article number e1009749.
The published version is available at https://doi.org/10.1371/journal.ppat.1009749
Copyright © 2021 Kervevan et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.