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IL-7 as an adjuvant for mucosal vaccine development

Title: IL-7 as an adjuvant for mucosal vaccine development
Authors: Rancez, Magali; Logerot, S; Figueiredo, S.; Charmeteau-De-Muylder, B; Bourgault-Villada, I; Couëdel-Courteille, A; Cheynier, R; Moraes-Cabe, Carolina
Contributors: Institut Cochin (IC UM3 (UMR 8104 / U1016)); Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Université Paris Diderot - Paris 7 (UPD7)
Source: 22nd International AIDS Conference (AIDS 2018); https://hal.science/hal-03000425; 22nd International AIDS Conference (AIDS 2018), Jul 2018, Amsterdam, Netherlands. 2018
Publisher Information: CCSD
Publication Year: 2018
Subject Terms: [SDV]Life Sciences [q-bio]
Subject Geographic: Amsterdam; Netherlands
Description: International audience ; Background: Despite considerable research efforts, mucosal immunity remains particularly difficult to stimulate through vaccines. Systemic injection of IL-7 stimulates chemokines-induced recruitment of circulating T-cells into mucosae.Methods: The optimal dose of IL-7 to be sprayed on mucosal surface was defined on 14 rhesus macaques. On mucosal biopsies collected after IL-7 administration, we quantified local transcription of 19 chemokines by qRT-PCR and cell infiltration by immunochemistry plus image analysis. Six macaques were immunized with antigens (DT and the HIV-1 gp41-P1 peptide) applied directly on the vaginal mucosa, two days after either IL-7 or PBS administration. The immunizations were repeated thrice, four months apart, and the macaques were euthanized 2 weeks after the last immunization. Antigen-specific IgA and IgG productions were quantified in vaginal secretions by ELISA. Antigen-specific plasma cells were detected by reverse immunohistochemistry in tissue, and by B-cell ELISPOT in PBMCs.Results: A significant overexpression of twelve chemokines was observed 48 hours after mucosal administration of 10µg of IL-7. Subsequently, mDC, macrophage, NK, B- and T-cell numbers significantly raised in the IL-7-treated mucosae, suggesting massive chemokine-driven infiltration. Administration of antigens led to a stronger mucosal immune response in the IL-7-treated macaques as compared to animals immunized with antigens alone. Robust production of antigen-specific IgAs and IgGs was detected in vaginal secretions. The immunizations repeated thrice sustained mucosal specific immune responses. Antigen-specific-antibody secreting cells were recovered from PBMC and more DT-specific plasma cells were found in the vaginal mucosae (IgA isotype) and the draining lymph nodes (IgG isotype) of IL-7-treated macaques. Tertiary lymphoid organs were observed in vaginal mucosae from IL-7-treated macaques only.Conclusions: Pre-treatment by non-traumatic vaginal administration of IL-7 (10µg by ...
Document Type: conference object; still image
Language: English
Availability: https://hal.science/hal-03000425; https://hal.science/hal-03000425v1/document; https://hal.science/hal-03000425v1/file/THPEA017_IL-7%20as%20an%20adjuvant%20for%20mucosal%20vaccine%20development_AIDS%202018_MRbis.pdf
Rights: info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.9C9134F6
Database: BASE