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The Protective HIV-1 Envelope gp41 Antigen P1 Acts as a Mucosal Adjuvant Stimulating the Innate Immunity
Mucosal nasal vaccine development, although ideal to protect from pathogens invading mucosally, is limited by the lack of specific adjuvant. We recently used P1, a conserved region of HIV-1 gp41-envelope glycoprotein, as efficient antigen in a prophylactic HIV-1 mucosal vaccine applied nasally. Here...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886812/ https://www.ncbi.nlm.nih.gov/pubmed/33613520 http://dx.doi.org/10.3389/fimmu.2020.599278 |
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author | Xu, Lin Tudor, Daniela Bomsel, Morgane |
author_facet | Xu, Lin Tudor, Daniela Bomsel, Morgane |
author_sort | Xu, Lin |
collection | PubMed |
description | Mucosal nasal vaccine development, although ideal to protect from pathogens invading mucosally, is limited by the lack of specific adjuvant. We recently used P1, a conserved region of HIV-1 gp41-envelope glycoprotein, as efficient antigen in a prophylactic HIV-1 mucosal vaccine applied nasally. Herein, P1 immunomodulation properties were assessed on human nasal mucosal models by measuring induction of cytokine and chemokine production, intracellular signaling pathways, mucosal dendritic cell (DC) activation, and T cell proliferation. P1 adjuvant properties were evaluated by quantification of antigen-specific B cell responses against a model antigen in an in vitro immunization model. We now demonstrated that P1 has additional immunological properties. P1 initiates immune responses by inducing nasal epithelial cells to secrete the Th2-cytokine thymic stromal lymphopoietin (TSLP), a described mucosal adjuvant. Secreted TSLP activates, in turn, intracellular calcium flux and PAR-2-associated NFAT signaling pathway regulated by microRNA-4485. Thereafter, P1 induces mucosal dendritic cell maturation, secretion of TSLP in a TSLP-receptor (R)-dependent autocrine loop, but also IL-6, IL-10, IL-8, CCL20, CCL22, and MMP-9, and proliferation of CD4+ T cells. Finally, P1 acts as an adjuvant to stimulate antigen-specific B cell responses in vitro. Overall, P1 is a multi-functional domain with various immuno-modulatory properties. In addition to being a protective vaccine antigen for HIV prevention, P1 acts as adjuvant for other mucosal vaccines able to stimulate humoral and cellular antigen-specific responses. |
format | Online Article Text |
id | pubmed-7886812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78868122021-02-18 The Protective HIV-1 Envelope gp41 Antigen P1 Acts as a Mucosal Adjuvant Stimulating the Innate Immunity Xu, Lin Tudor, Daniela Bomsel, Morgane Front Immunol Immunology Mucosal nasal vaccine development, although ideal to protect from pathogens invading mucosally, is limited by the lack of specific adjuvant. We recently used P1, a conserved region of HIV-1 gp41-envelope glycoprotein, as efficient antigen in a prophylactic HIV-1 mucosal vaccine applied nasally. Herein, P1 immunomodulation properties were assessed on human nasal mucosal models by measuring induction of cytokine and chemokine production, intracellular signaling pathways, mucosal dendritic cell (DC) activation, and T cell proliferation. P1 adjuvant properties were evaluated by quantification of antigen-specific B cell responses against a model antigen in an in vitro immunization model. We now demonstrated that P1 has additional immunological properties. P1 initiates immune responses by inducing nasal epithelial cells to secrete the Th2-cytokine thymic stromal lymphopoietin (TSLP), a described mucosal adjuvant. Secreted TSLP activates, in turn, intracellular calcium flux and PAR-2-associated NFAT signaling pathway regulated by microRNA-4485. Thereafter, P1 induces mucosal dendritic cell maturation, secretion of TSLP in a TSLP-receptor (R)-dependent autocrine loop, but also IL-6, IL-10, IL-8, CCL20, CCL22, and MMP-9, and proliferation of CD4+ T cells. Finally, P1 acts as an adjuvant to stimulate antigen-specific B cell responses in vitro. Overall, P1 is a multi-functional domain with various immuno-modulatory properties. In addition to being a protective vaccine antigen for HIV prevention, P1 acts as adjuvant for other mucosal vaccines able to stimulate humoral and cellular antigen-specific responses. Frontiers Media S.A. 2021-02-03 /pmc/articles/PMC7886812/ /pubmed/33613520 http://dx.doi.org/10.3389/fimmu.2020.599278 Text en Copyright © 2021 Xu, Tudor and Bomsel http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Xu, Lin Tudor, Daniela Bomsel, Morgane The Protective HIV-1 Envelope gp41 Antigen P1 Acts as a Mucosal Adjuvant Stimulating the Innate Immunity |
title | The Protective HIV-1 Envelope gp41 Antigen P1 Acts as a Mucosal Adjuvant Stimulating the Innate Immunity |
title_full | The Protective HIV-1 Envelope gp41 Antigen P1 Acts as a Mucosal Adjuvant Stimulating the Innate Immunity |
title_fullStr | The Protective HIV-1 Envelope gp41 Antigen P1 Acts as a Mucosal Adjuvant Stimulating the Innate Immunity |
title_full_unstemmed | The Protective HIV-1 Envelope gp41 Antigen P1 Acts as a Mucosal Adjuvant Stimulating the Innate Immunity |
title_short | The Protective HIV-1 Envelope gp41 Antigen P1 Acts as a Mucosal Adjuvant Stimulating the Innate Immunity |
title_sort | protective hiv-1 envelope gp41 antigen p1 acts as a mucosal adjuvant stimulating the innate immunity |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886812/ https://www.ncbi.nlm.nih.gov/pubmed/33613520 http://dx.doi.org/10.3389/fimmu.2020.599278 |
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