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Plant-made virus-like particles bearing influenza hemagglutinin (HA) recapitulate early interactions of native influenza virions with human monocytes/macrophages

•In addition to antibodies, plant-made VLP vaccines elicit an unusually strong CD4+ T cell response.•These enveloped VLPs recapitulate several key features of the initial virus-APC interactions.•Similarities of VLP/virus-cell interactions may help to explain the unusual features of the immune respon... Full description

Journal Title: Vaccine 2017, Vol.35 (35), p.4629-4636
Main Author: Makarkov, Alexander I
Other Authors: Chierzi, Sabrina , Pillet, Stéphane , Murai, Keith K , Landry, Nathalie , Ward, Brian J
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
Link: https://www.ncbi.nlm.nih.gov/pubmed/28712489
Zum Text:
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title: Plant-made virus-like particles bearing influenza hemagglutinin (HA) recapitulate early interactions of native influenza virions with human monocytes/macrophages
format: Article
creator:
  • Makarkov, Alexander I
  • Chierzi, Sabrina
  • Pillet, Stéphane
  • Murai, Keith K
  • Landry, Nathalie
  • Ward, Brian J
subjects:
  • Acids
  • Analysis
  • Antigen processing
  • Antigen-presenting cells
  • Antigens
  • Avian flu
  • Avian influenza
  • Blood & organ donations
  • Cell fusion
  • Cell proliferation
  • Cell surface
  • Cholera toxin
  • Cloning
  • Compartments
  • Dendritic cells
  • Experiments
  • Hemagglutinins
  • Human monocyte-derived macrophage
  • Immunity
  • Immunogenicity
  • Immunological memory
  • Incubation
  • Infections
  • Influenza
  • Influenza vaccines
  • Influenza viruses
  • Internalization
  • Lectins
  • Leukocytes (mononuclear)
  • Lymphocytes T
  • Macrophages
  • Membranes
  • Microscopy
  • Monocytes
  • Peripheral blood mononuclear cells
  • Plant viruses
  • Plant-made vaccine
  • Proteins
  • Sialic acids
  • Stimulation
  • T cells
  • U-937 cell line
  • Vaccines
  • Virions
  • Virus-like particle
  • Virus-like particles
  • Viruses
ispartof: Vaccine, 2017, Vol.35 (35), p.4629-4636
description: •In addition to antibodies, plant-made VLP vaccines elicit an unusually strong CD4+ T cell response.•These enveloped VLPs recapitulate several key features of the initial virus-APC interactions.•Similarities of VLP/virus-cell interactions may help to explain the unusual features of the immune response induced. Plant-made virus-like particles (VLP) bearing influenza virus hemagglutinins (HA) are novel vaccine candidates that induce cross-reactive humoral and poly-functional T cell responses. To better understand the mechanisms that underlie this broad immunogenicity we studied early interactions of VLPs bearing either H1 (A/California/07/2009 (H1N1)) or H5 (A/Indonesia/05/2005 (H5N1)) with a human monocytoid cell line (U-937 cells) and human monocyte-derived macrophages (MDMs) as model antigen-presenting cells (APC). Using Vibrio cholerae sialidase and lectins that target α2,6- (Sambucus nigra lectin) or α2,3-linked sialic acids (Maackia amurensis lectin I), we demonstrated that VLPs bind to these APCs in a sialic acid-dependent manner. Using lysosomal markers and DiD-labelled VLPs, we found that attachment to the cell surface leads to internalization, trafficking to acidic cell compartments and fusion of the VLP lipid envelope with endosomal membranes. Incubation of MDMs with H1- but not H5-VLPs induced proliferation of autologous peripheral blood mononuclear cells suggesting antigen processing and stimulation of a memory T cell response. Plant-made VLPs bearing influenza HA not only mimic the structure of influenza virions to some degree but also recapitulate key features of the initial virus-APC interaction. These observations may help to explain the balanced humoral and cellular responses to plant-made VLP vaccines.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0264-410X
fulltext: fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


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titlePlant-made virus-like particles bearing influenza hemagglutinin (HA) recapitulate early interactions of native influenza virions with human monocytes/macrophages
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creatorMakarkov, Alexander I ; Chierzi, Sabrina ; Pillet, Stéphane ; Murai, Keith K ; Landry, Nathalie ; Ward, Brian J
creatorcontribMakarkov, Alexander I ; Chierzi, Sabrina ; Pillet, Stéphane ; Murai, Keith K ; Landry, Nathalie ; Ward, Brian J
description•In addition to antibodies, plant-made VLP vaccines elicit an unusually strong CD4+ T cell response.•These enveloped VLPs recapitulate several key features of the initial virus-APC interactions.•Similarities of VLP/virus-cell interactions may help to explain the unusual features of the immune response induced. Plant-made virus-like particles (VLP) bearing influenza virus hemagglutinins (HA) are novel vaccine candidates that induce cross-reactive humoral and poly-functional T cell responses. To better understand the mechanisms that underlie this broad immunogenicity we studied early interactions of VLPs bearing either H1 (A/California/07/2009 (H1N1)) or H5 (A/Indonesia/05/2005 (H5N1)) with a human monocytoid cell line (U-937 cells) and human monocyte-derived macrophages (MDMs) as model antigen-presenting cells (APC). Using Vibrio cholerae sialidase and lectins that target α2,6- (Sambucus nigra lectin) or α2,3-linked sialic acids (Maackia amurensis lectin I), we demonstrated that VLPs bind to these APCs in a sialic acid-dependent manner. Using lysosomal markers and DiD-labelled VLPs, we found that attachment to the cell surface leads to internalization, trafficking to acidic cell compartments and fusion of the VLP lipid envelope with endosomal membranes. Incubation of MDMs with H1- but not H5-VLPs induced proliferation of autologous peripheral blood mononuclear cells suggesting antigen processing and stimulation of a memory T cell response. Plant-made VLPs bearing influenza HA not only mimic the structure of influenza virions to some degree but also recapitulate key features of the initial virus-APC interaction. These observations may help to explain the balanced humoral and cellular responses to plant-made VLP vaccines.
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languageeng
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subjectAcids ; Analysis ; Antigen processing ; Antigen-presenting cells ; Antigens ; Avian flu ; Avian influenza ; Blood & organ donations ; Cell fusion ; Cell proliferation ; Cell surface ; Cholera toxin ; Cloning ; Compartments ; Dendritic cells ; Experiments ; Hemagglutinins ; Human monocyte-derived macrophage ; Immunity ; Immunogenicity ; Immunological memory ; Incubation ; Infections ; Influenza ; Influenza vaccines ; Influenza viruses ; Internalization ; Lectins ; Leukocytes (mononuclear) ; Lymphocytes T ; Macrophages ; Membranes ; Microscopy ; Monocytes ; Peripheral blood mononuclear cells ; Plant viruses ; Plant-made vaccine ; Proteins ; Sialic acids ; Stimulation ; T cells ; U-937 cell line ; Vaccines ; Virions ; Virus-like particle ; Virus-like particles ; Viruses
ispartofVaccine, 2017, Vol.35 (35), p.4629-4636
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0Acids
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4Antigens
5Avian flu
6Avian influenza
7Blood & organ donations
8Cell fusion
9Cell proliferation
10Cell surface
11Cholera toxin
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13Compartments
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15Experiments
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17Human monocyte-derived macrophage
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19Immunogenicity
20Immunological memory
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29Lymphocytes T
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abstract•In addition to antibodies, plant-made VLP vaccines elicit an unusually strong CD4+ T cell response.•These enveloped VLPs recapitulate several key features of the initial virus-APC interactions.•Similarities of VLP/virus-cell interactions may help to explain the unusual features of the immune response induced. Plant-made virus-like particles (VLP) bearing influenza virus hemagglutinins (HA) are novel vaccine candidates that induce cross-reactive humoral and poly-functional T cell responses. To better understand the mechanisms that underlie this broad immunogenicity we studied early interactions of VLPs bearing either H1 (A/California/07/2009 (H1N1)) or H5 (A/Indonesia/05/2005 (H5N1)) with a human monocytoid cell line (U-937 cells) and human monocyte-derived macrophages (MDMs) as model antigen-presenting cells (APC). Using Vibrio cholerae sialidase and lectins that target α2,6- (Sambucus nigra lectin) or α2,3-linked sialic acids (Maackia amurensis lectin I), we demonstrated that VLPs bind to these APCs in a sialic acid-dependent manner. Using lysosomal markers and DiD-labelled VLPs, we found that attachment to the cell surface leads to internalization, trafficking to acidic cell compartments and fusion of the VLP lipid envelope with endosomal membranes. Incubation of MDMs with H1- but not H5-VLPs induced proliferation of autologous peripheral blood mononuclear cells suggesting antigen processing and stimulation of a memory T cell response. Plant-made VLPs bearing influenza HA not only mimic the structure of influenza virions to some degree but also recapitulate key features of the initial virus-APC interaction. These observations may help to explain the balanced humoral and cellular responses to plant-made VLP vaccines.
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pmid28712489
doi10.1016/j.vaccine.2017.07.012