title: MPLA-coated hepatitis B virus surface antigen (HBsAg) nanocapsules induce vigorous T cell responses in cord blood derived human T cells.
abstract: Chronic hepatitis B virus (HBV) infection is the most prevalent serious liver infection in the world. A frequent route of infection represents mother-to-child transmission. Efficient control of HBV replication depends on antigen-specific cellular immune response mediated by dendritic cells (DCs). Aim of the present study was to evaluate optimized adjuvant combinations, efficiently maturing monocyte-derived neonatal and adult dendritic cells (moDCs). In addition, the potential of polymeric HBsAg-nanocapsules (HBsAg-NCs) was investigated regarding up-take by moDCs and the subsequent induction of specific T cell responses in a human co-culture model. Simultaneous stimulation of moDCs with MPLA and IFNγ induced up-regulation of CD80 and HLA-DR along with vigorous secretion of IL-12p70. MPLA-coating of HBsAg-NCs promoted NCs-uptake by moDCs. Finally, MPLA-HBsAg-NCs-pulsed moDCs with IFNγ increased T cell proliferation and induced antigen-specific IFNγ release by T cells. The herein presented vaccine approach provides a rational for neonatal and therapeutic immunization strategies against HBV.
authors: Children's Hospital, University Medical Center, Johannes-Gutenberg University, Mainz, Germany.
authors: Anette
authors: A
authors: Pietrzak-Nguyen
authors: Max Planck Institute for Polymer research, Mainz, Germany.
authors: Keti
authors: K
authors: Piradashvili
authors: Children's Hospital, University Medical Center, Johannes-Gutenberg University, Mainz, Germany.
authors: Michael
authors: M
authors: Fichter
authors: Children's Hospital, University Medical Center, Johannes-Gutenberg University, Mainz, Germany.
authors: Leah
authors: L
authors: Pretsch
authors: Children's Hospital, University Medical Center, Johannes-Gutenberg University, Mainz, Germany.
authors: Fred
authors: F
authors: Zepp
authors: Max Planck Institute for Polymer research, Mainz, Germany.
authors: Frederik R
authors: FR
authors: Wurm
authors: Max Planck Institute for Polymer research, Mainz, Germany.
authors: Katharina
authors: K
authors: Landfester
authors: Children's Hospital, University Medical Center, Johannes-Gutenberg University, Mainz, Germany. Electronic address: stephan.gehring@uni-mainz.de.
authors: Stephan
authors: S
authors: Gehring
mesh_terms: D000954:Antigens, Surface; D003713:Dendritic Cells; D005312:Fetal Blood; D006509:Hepatitis B / Q000517:prevention & control; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D006515:Hepatitis B virus; D006801:Humans; D053769:Nanocapsules; D013601:T-Lymphocytes
chemical_list: D000954:Antigens, Surface; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D053769:Nanocapsules
keywords: Co-culture model; HBsAg nanocapsules; MPLA and IFNγ stimulation; Neonatal moDCs; T(H)1 immune response