MPLA-coated hepatitis B virus surface antigen (HBsAg) nanocapsules induce vigorous T cell responses in cord blood derived human T cells

作者:Pietrzak Nguyen Anette; Piradashvili Keti; Fichter Michael; Pretsch Leah; Zepp Fred; Wurm Frederik R; Landfester Katharina; Gehring Stephan*
来源:Nanomedicine: Nanotechnology, Biology and Medicine , 2016, 12(8): 2383-2394.
DOI:10.1016/j.nano.2016.07.010

摘要

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 IFN gamma 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 IFN gamma increased T cell proliferation and induced antigen-specific IFN gamma release by T cells. The herein presented vaccine approach provides a rational for neonatal and therapeutic immunization strategies against HBV.

  • 出版日期2016-11