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Human immunodeficiency virus type-1 (HIV-1) Pr55gag virus-like particles are potent activators of human monocytes
Authors:Speth Cornelia  Bredl Simon  Hagleitner Magdalena  Wild Jens  Dierich Manfred  Wolf Hans  Schroeder Josef  Wagner Ralf  Deml Ludwig
Affiliation:a Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, Innsbruck, Austria
b Institute of Medical Microbiology, University of Regensburg, Franz-Josef-Strauss Allee 11, D-93053, Regensburg, Germany
c Institute of Pathology, central EM-Lab, University of Regensburg, Regensburg, Germany
Abstract:Human immunodeficiency virus type-1 (HIV-1) Pr55Gag virus-like particles (VLP) represent an interesting HIV vaccine component since they stimulate strong humoral and cellular immune responses. We demonstrated that VLP expressed by recombinant baculoviruses activate human PBMC to release pro-inflammatory (lL-6, TNF-α), anti-inflammatory (IL-10) and Th1-polarizing (IFN-γ) cytokines as well as GM-CSF and MIP-1α in a dose-and time-dependent manner. Herein, residual baculoviruses within the VLP preparations showed no or minor effects. Monocytes could be identified as a main target for VLP to induce cytokine production. Furthermore, VLP-induced monocyte activation was shown by upregulation of molecules involved in antigen presentation (MHC II, CD80, CD86) and cell adhesion (CD54). Exposure of VLP to serum inactivates its capacity to stimulate cytokine production. In summary, these investigations establish VLP as strong activators of PBMC and monocytes therein, potently enhancing their functionality and potency to promote an efficient immune response. This capacity makes VLP an interesting component of combination vaccines.
Keywords:Virus-like particles   Cytokines   Innate immunity   Monocytes   PBMC
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