Malherbe Delphine C, Domi Arban, Hauser Mary J, Meyer Michelle, Gunn Bronwyn M, Alter Galit, Bukreyev Alexander, Guirakhoo Farshad
Department of Pathology, University of Texas Medical Branch, Galveston, TX USA.
Galveston National Laboratory, Galveston, TX USA.
NPJ Vaccines. 2020 Sep 2;5(1):78. doi: 10.1038/s41541-020-00226-y. eCollection 2020.
We introduce a new vaccine platform against Marburg virus (MARV) combining the advantages of the immunogenicity of a highly attenuated vaccine vector (Modified Vaccinia Ankara, MVA) with the authentic conformation of virus-like particles (VLPs). Our vaccine, MVA-MARV-VLP, expresses the minimal components of MARV VLPs: the envelope glycoprotein GP and the matrix protein VP40. Electron microscopy confirmed self-assembly and budding of VLPs from infected cells. Prime/boost vaccination of guinea pigs with MVA-MARV-VLP-elicited MARV-specific binding and neutralizing antibody responses. Vaccination also induced Fc-mediated innate immune effector functions including activation of NK cells and antibody-dependent phagocytosis by neutrophils and monocytes. Inoculation of vaccinated animals with guinea pig-adapted MARV demonstrated 100% protection against death and disease with no viremia. Therefore, our vaccine platform, expressing two antigens resulting in assembly of VLPs in the native conformation in vaccinated hosts, can be used as a potent vaccine against MARV.
我们推出了一种针对马尔堡病毒（MARV）的新型疫苗平台，该平台结合了高度减毒疫苗载体（安卡拉痘苗病毒，MVA）的免疫原性优势与病毒样颗粒（VLPs）的真实构象。我们的疫苗MVA-MARV-VLP表达了MARV VLPs的最小组成成分：包膜糖蛋白GP和基质蛋白VP40。电子显微镜证实了VLPs从受感染细胞中自组装和出芽。用MVA-MARV-VLP对豚鼠进行初免/加强免疫可引发针对MARV的特异性结合和中和抗体反应。疫苗接种还诱导了Fc介导的先天性免疫效应功能，包括NK细胞的激活以及中性粒细胞和单核细胞的抗体依赖性吞噬作用。用适应豚鼠的MARV接种已接种疫苗的动物，结果显示100%的动物得到保护，免于死亡和疾病，且无病毒血症。因此，我们的疫苗平台在接种宿主中表达两种抗原，导致以天然构象组装VLPs，可作为一种有效的抗MARV疫苗。
