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

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• 作者：Anette Pietrzak-Nguyen ; MSc^a ; Keti Piradashvili ; MSc^b ; Michael Fichter ; MSc^a ; Leah Pretsch^a ; Fred Zepp ; MD^a ; Frederik R. Wurm ; PhD^b ; Katharina Landfester ; PhD^b ; Stephan Gehring ; MD^a ; ^{stephan.gehring@uni-mainz.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Neonatal moDCs ; MPLA and IFNγ stimulation ; HBsAg nanocapsules ; Co-culture model ; TH1 immune response
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：12
• 期：8
• 页码：2383-2394
• 全文大小：1885 K

文摘

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.