Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity

Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity

Vaccines aiming to promote T-cell-mediated immune responses have so far showed limited efficacy, and there is a need for novel strategies. Studies indicate that autophagy plays an inherent role in antigen processing and presentation for CD4+ and CD8+ T cells. Here, we report a novel vaccine strategy...

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Main Authors: Andersen, Aram Nikolai, Landsverk, Ole Jørgen, Simonsen, Anne, Bogen, Bjarne, Corthay, Alexandre, Øynebråten, Inger
Format: Online
Language:English
Published: Frontiers Media S.A. 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861724/
id pubmed-4861724
recordtype oai_dc
spelling pubmed-48617242016-05-30 Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity Andersen, Aram Nikolai Landsverk, Ole Jørgen Simonsen, Anne Bogen, Bjarne Corthay, Alexandre Øynebråten, Inger Immunology Vaccines aiming to promote T-cell-mediated immune responses have so far showed limited efficacy, and there is a need for novel strategies. Studies indicate that autophagy plays an inherent role in antigen processing and presentation for CD4+ and CD8+ T cells. Here, we report a novel vaccine strategy based on fusion of antigen to the selective autophagy receptor sequestosome 1 (SQSTM1)/p62. We hypothesized that redirection of vaccine antigen from proteasomal degradation into the autophagy pathway would increase the generation of antigen-specific T cells. A hybrid vaccine construct was designed in which the antigen is fused to the C-terminus of p62, a signaling hub, and a receptor that naturally delivers ubiquitinated cargo for autophagic degradation. Fusion of the human immunodeficiency virus-1 antigen Gagp24 to p62 resulted in efficient antigen delivery into the autophagy pathway. Intradermal immunization of mice revealed that, in comparison to Gagp24 delivered alone, fusion to p62 enhanced the number of Gagp24-specific interferon-γ-producing T cells, including CD8+ T cells. The strategy may also have the potential to modulate the antigenic peptide repertoire. Because p62 and autophagy are highly conserved between species, we anticipate this strategy to be a candidate for the development of T-cell-based vaccines in humans. Frontiers Media S.A. 2016-05-10 /pmc/articles/PMC4861724/ /pubmed/27242780 http://dx.doi.org/10.3389/fimmu.2016.00167 Text en Copyright © 2016 Andersen, Landsverk, Simonsen, Bogen, Corthay and Øynebråten. 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) or licensor 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.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Andersen, Aram Nikolai
Landsverk, Ole Jørgen
Simonsen, Anne
Bogen, Bjarne
Corthay, Alexandre
Øynebråten, Inger
spellingShingle Andersen, Aram Nikolai
Landsverk, Ole Jørgen
Simonsen, Anne
Bogen, Bjarne
Corthay, Alexandre
Øynebråten, Inger
Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity
author_facet Andersen, Aram Nikolai
Landsverk, Ole Jørgen
Simonsen, Anne
Bogen, Bjarne
Corthay, Alexandre
Øynebråten, Inger
author_sort Andersen, Aram Nikolai
title Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity
title_short Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity
title_full Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity
title_fullStr Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity
title_full_unstemmed Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity
title_sort coupling of hiv-1 antigen to the selective autophagy receptor sqstm1/p62 promotes t-cell-mediated immunity
description Vaccines aiming to promote T-cell-mediated immune responses have so far showed limited efficacy, and there is a need for novel strategies. Studies indicate that autophagy plays an inherent role in antigen processing and presentation for CD4+ and CD8+ T cells. Here, we report a novel vaccine strategy based on fusion of antigen to the selective autophagy receptor sequestosome 1 (SQSTM1)/p62. We hypothesized that redirection of vaccine antigen from proteasomal degradation into the autophagy pathway would increase the generation of antigen-specific T cells. A hybrid vaccine construct was designed in which the antigen is fused to the C-terminus of p62, a signaling hub, and a receptor that naturally delivers ubiquitinated cargo for autophagic degradation. Fusion of the human immunodeficiency virus-1 antigen Gagp24 to p62 resulted in efficient antigen delivery into the autophagy pathway. Intradermal immunization of mice revealed that, in comparison to Gagp24 delivered alone, fusion to p62 enhanced the number of Gagp24-specific interferon-γ-producing T cells, including CD8+ T cells. The strategy may also have the potential to modulate the antigenic peptide repertoire. Because p62 and autophagy are highly conserved between species, we anticipate this strategy to be a candidate for the development of T-cell-based vaccines in humans.
publisher Frontiers Media S.A.
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861724/
_version_ 1613577313294745600

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