In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 7 ( 2021-7-29), p. e1009749-
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009749
DOI:
10.1371/journal.ppat.1009749.g001
DOI:
10.1371/journal.ppat.1009749.g002
DOI:
10.1371/journal.ppat.1009749.g003
DOI:
10.1371/journal.ppat.1009749.g004
DOI:
10.1371/journal.ppat.1009749.g005
DOI:
10.1371/journal.ppat.1009749.s001
DOI:
10.1371/journal.ppat.1009749.s002
DOI:
10.1371/journal.ppat.1009749.s003
DOI:
10.1371/journal.ppat.1009749.s004
DOI:
10.1371/journal.ppat.1009749.s005
DOI:
10.1371/journal.ppat.1009749.s006
DOI:
10.1371/journal.ppat.1009749.s007
DOI:
10.1371/journal.ppat.1009749.s008
DOI:
10.1371/journal.ppat.1009749.s009
DOI:
10.1371/journal.ppat.1009749.s010
DOI:
10.1371/journal.ppat.1009749.s011
DOI:
10.1371/journal.ppat.1009749.s012
DOI:
10.1371/journal.ppat.1009749.s013
DOI:
10.1371/journal.ppat.1009749.s014
DOI:
10.1371/journal.ppat.1009749.r001
DOI:
10.1371/journal.ppat.1009749.r002
DOI:
10.1371/journal.ppat.1009749.r003
DOI:
10.1371/journal.ppat.1009749.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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