TY - JOUR
T1 - MPLA-coated hepatitis B virus surface antigen (HBsAg) nanocapsules induce vigorous T cell responses in cord blood derived human T cells
AU - Pietrzak-Nguyen, Anette
AU - Piradashvili, Keti
AU - Fichter, Michael
AU - Pretsch, Leah
AU - Zepp, Fred
AU - Wurm, Frederik R.
AU - Landfester, Katharina
AU - Gehring, Stephan
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - Co-culture model
KW - HBsAg nanocapsules
KW - MPLA and IFNγ stimulation
KW - Neonatal moDCs
KW - T1 immune response
UR - http://www.scopus.com/inward/record.url?scp=84983643630&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2016.07.010
DO - 10.1016/j.nano.2016.07.010
M3 - Article
C2 - 27516081
AN - SCOPUS:84983643630
VL - 12
SP - 2383
EP - 2394
JO - Nanomedicine : nanotechnology, biology and medicine
JF - Nanomedicine : nanotechnology, biology and medicine
SN - 1549-9634
IS - 8
ER -