Medical Clinic and Policlinic II, Department of Hematology, Julius Maximilians University of Würzburg, Würzburg, Germany.
Cytotherapy. 2011 Jul;13(6):739-52. doi: 10.3109/14653249.2010.549123. Epub 2011 Jan 20.
Modified vaccinia Ankara (MVA) is a promising vaccine vector for infectious diseases and malignancies. It is fundamental to ascertain its tropism in human leukocyte populations and immunostimulatory mechanisms for application in immunotherapy.
Human peripheral blood mononuclear cells (PBMC) and leukocyte subpopulations [monocyte-derived dendritic cells (DC), monocytes and B cells] were infected with MVA in order to evaluate their infection rate, changes in surface markers, cytokine expression and apoptosis.
Monocytes, DC and B cells were most susceptible to MVA infection, followed by natural killer (NK) cells. Monocytes were activated strongly, with upregulation of co-stimulatory molecules, major histocompatibility complex (MHC) molecules and chemokine (C-C motif) receptor (CCR7), while immature DC showed partial activation and B cells were inhibited. Furthermore, expression of chemokine (C-X-C motif) ligand (CXCL10), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12p70 was enhanced but IL-1β and IL-10 were stable or even downregulated. MVA induced a high apoptosis rate of antigen-presenting cells (APC). Nevertheless, incubation of MVA-infected leukocytes with uninfected immature DC (iDC) led to complete maturation of the DC. Subsequently, the matured DC were able to stimulate cytomegalovirus (CMV)-immediate early protein (IE1)-specific T cells.
MVA induces a T-helper (Th)-1-polarizing cytokine expression in APC. Furthermore, incubation of MVA-infected leukocytes with uninfected iDC leads to complete maturation of the DC and may be the basis for cross-presentation of MVA-encoded antigens. Thus this approach seems to be an ideal model for further studies with MVA-encoded viral antigens regarding immunotherapy and vaccination strategies.
改良安卡拉牛痘病毒（MVA）是一种很有前途的传染病和恶性肿瘤的疫苗载体。确定其在人类白细胞群体中的趋向性以及免疫刺激机制对于应用于免疫治疗至关重要。
用人外周血单核细胞（PBMC）和白细胞亚群（单核细胞衍生的树突状细胞（DC）、单核细胞和 B 细胞）感染 MVA，以评估其感染率、表面标志物变化、细胞因子表达和细胞凋亡。
单核细胞、DC 和 B 细胞对 MVA 的感染最敏感，其次是自然杀伤（NK）细胞。单核细胞被强烈激活，共刺激分子、主要组织相容性复合体（MHC）分子和趋化因子（C-C 基序）受体（CCR7）上调，而不成熟的 DC 表现出部分激活，B 细胞受到抑制。此外，趋化因子（C-X-C 基序）配体（CXCL10）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6 和 IL-12p70 的表达增强，但 IL-1β 和 IL-10 保持稳定甚至下调。MVA 诱导抗原呈递细胞（APC）的高凋亡率。然而，用未感染的不成熟树突状细胞（iDC）孵育感染 MVA 的白细胞会导致 DC 的完全成熟。随后，成熟的 DC 能够刺激巨细胞病毒（CMV）立即早期蛋白（IE1）特异性 T 细胞。
MVA 在 APC 中诱导 Th1 极化细胞因子表达。此外，用未感染的 iDC 孵育感染 MVA 的白细胞会导致 DC 的完全成熟，这可能是 MVA 编码抗原交叉呈递的基础。因此，这种方法似乎是进一步研究 MVA 编码病毒抗原的免疫治疗和疫苗接种策略的理想模型。
