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

Nanomedicine. 2016 Nov;12(8):2383-2394. doi: 10.1016/j.nano.2016.07.010. Epub 2016 Aug 8.

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.

Keywords: Co-culture model; HBsAg nanocapsules; MPLA and IFNγ stimulation; Neonatal moDCs; T(H)1 immune response.

MeSH terms

  • Antigens, Surface
  • Dendritic Cells
  • Fetal Blood*
  • Hepatitis B / prevention & control
  • Hepatitis B Surface Antigens*
  • Hepatitis B Vaccines*
  • Hepatitis B virus
  • Humans
  • Nanocapsules*
  • T-Lymphocytes*

Substances

  • Antigens, Surface
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Nanocapsules