Document Type
Article
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
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
34324611
Language
English
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.