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Loading dendritic cells with PLA-p24 nanoparticles or MVA expressing HIV genes induces HIV-1-specific T cell responses.

Abstract
Since recent data suggest that nanoparticles and modified vaccinia ankara (MVA) vectors could play a pivotal role in HIV-1 therapeutics and vaccine design, in an ex vivo model of human monocyte-derived dendritic cells (MDDCs), we compared two different loading strategies with HIV-1 vaccine vehicles, either viral or synthetic derived. We used polylactic acid (PLA) colloidal biodegradable particles, coated with HIV Gag antigens (p24), and MVA expressing Gag (rMVA-gag and rMVA-gag/trans membrane) or Tat, Nef and Rev genes (rMVA tat+rev and rMVA nef). PLA-p24 captured by MDDCs from HIV-1 individuals induced a slight degree of MDDC maturation, cytokine and chemokine secretion and migration towards a gradient of CCL19 chemokine and highly increased HIV-specific CD8(+) T-cell proliferation compared with p24 alone. After complete maturation induction of PLA-p24-pulsed MDDCs, maximal migration towards a gradient of CCL19 chemokine and induction of HIV-specific T-cell proliferation (two-fold higher for CD4(+) than CD8(+)) and cytokine secretion (IFN-γ and IL-2) in the co-culture were observed. Upon exposure to MVA-gag, MDDCs produced cytokines and chemokines and maintained their capacity to migrate to a gradient of CCL19. MDDCs infected with MVA-gag and MVA-gag trans-membrane were able to induce HIV-specific CD8(+) proliferation and secretion of IFN-γ, IL-2, IL-6 and TNF-α. We conclude that both HIV antigens loading strategies (PLA-p24 nanoparticles or MVA expressing HIV genes) induce HIV-1-specific T-cell responses, which are able to kill autologous gag-expressing cells. Thus, they are plausible candidates for the development of anti-HIV vaccines.
AuthorsNúria Climent, Séverine Munier, Núria Piqué, Felipe García, Vincent Pavot, Charlotte Primard, Victor Casanova, José María Gatell, Bernard Verrier, Teresa Gallart
JournalVaccine (Vaccine) Vol. 32 Issue 47 Pg. 6266-76 (Oct 29 2014) ISSN: 1873-2518 [Electronic] Netherlands
PMID25240755 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • AIDS Vaccines
  • CCL19 protein, human
  • Chemokine CCL19
  • HIV Antigens
  • HIV Core Protein p24
  • IFNG protein, human
  • IL2 protein, human
  • Interleukin-2
  • Polymers
  • Vaccines, Synthetic
  • p24 protein, Human Immunodeficiency Virus Type 1
  • poly(lactic acid)
  • Lactic Acid
  • Interferon-gamma
Topics
  • AIDS Vaccines (immunology)
  • CD8-Positive T-Lymphocytes (immunology)
  • Cell Movement
  • Cells, Cultured
  • Chemokine CCL19 (immunology)
  • Coculture Techniques
  • Dendritic Cells (immunology)
  • HIV Antigens (immunology)
  • HIV Core Protein p24 (immunology)
  • HIV Infections (prevention & control)
  • HIV-1
  • Humans
  • Interferon-gamma (immunology)
  • Interleukin-2 (immunology)
  • Lactic Acid (pharmacology)
  • Nanoparticles
  • Polymers (pharmacology)
  • Vaccines, Synthetic (immunology)
  • Vaccinia virus (immunology)

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