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Andersen AN, Landsverk OJ, Simonsen A, et al. Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity. Front Immunol. 2016;7:167doi: 10.3389/fimmu.2016.00167.
Andersen, A. N., Landsverk, O. J., Simonsen, A., Bogen, B., Corthay, A., & Øynebråten, I. (2016). Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity. Frontiers in immunology, 7167. https://doi.org/10.3389/fimmu.2016.00167
Andersen, Aram Nikolai, et al. "Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity." Frontiers in immunology vol. 7 (2016): 167. doi: https://doi.org/10.3389/fimmu.2016.00167
Andersen AN, Landsverk OJ, Simonsen A, Bogen B, Corthay A, Øynebråten I. Coupling of HIV-1 Antigen to the Selective Autophagy Receptor SQSTM1/p62 Promotes T-Cell-Mediated Immunity. Front Immunol. 2016 May 10;7:167. doi: 10.3389/fimmu.2016.00167. eCollection 2016. PMID: 27242780; PMCID: PMC4861724.
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Front Immunol. 2016 May 10;7:167. doi: 10.3389/fimmu.2016.00167. eCollection 2016.

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

Frontiers in immunology

Aram Nikolai Andersen, Ole Jørgen Landsverk, Anne Simonsen, Bjarne Bogen, Alexandre Corthay, Inger Øynebråten

Affiliations

  1. Tumor Immunology Group, Department of Pathology, Rikshospitalet, University of Oslo and Oslo University Hospital, Oslo, Norway; Department of Immunology, Rikshospitalet, University of Oslo and Oslo University Hospital, Oslo, Norway.
  2. Centre for Immune Regulation, University of Oslo, Oslo, Norway; LIIPAT, Department of Pathology, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
  3. Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo , Oslo , Norway.
  4. Department of Immunology, Rikshospitalet, University of Oslo and Oslo University Hospital, Oslo, Norway; Centre for Immune Regulation, University of Oslo, Oslo, Norway; K. G. Jebsen Centre for Influenza Research, University of Oslo, Oslo, Norway.
  5. Tumor Immunology Group, Department of Pathology, Rikshospitalet, University of Oslo and Oslo University Hospital , Oslo , Norway.

PMID: 27242780 PMCID: PMC4861724 DOI: 10.3389/fimmu.2016.00167

Abstract

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.

Keywords: HIV-1 gagp24 antigen; T cell responses; autophagy; p62/SQSTM1; vaccine

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