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A vaccinia-based single vector construct multi-pathogen vaccine protects against both Zika and chikungunya viruses

机译:基于牛痘的单一载体构建多病原体疫苗可同时预防寨卡病毒和基孔肯雅病毒

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摘要

Zika and chikungunya viruses have caused major epidemics and are transmitted by Aedes aegypti and/or Aedes albopictus mosquitoes. The “Sementis Copenhagen Vector” (SCV) system is a recently developed vaccinia-based, multiplication-defective, vaccine vector technology that allows manufacture in modified CHO cells. Herein we describe a single-vector construct SCV vaccine that encodes the structural polyprotein cassettes of both Zika and chikungunya viruses from different loci. A single vaccination of mice induces neutralizing antibodies to both viruses in wild-type and IFNAR−/− mice and protects against (i) chikungunya virus viremia and arthritis in wild-type mice, (ii) Zika virus viremia and fetal/placental infection in female IFNAR−/− mice, and (iii) Zika virus viremia and testes infection and pathology in male IFNAR−/− mice. To our knowledge this represents the first single-vector construct, multi-pathogen vaccine encoding large polyproteins, and offers both simplified manufacturing and formulation, and reduced “shot burden” for these often co-circulating arboviruses.
机译:寨卡病毒和基孔肯雅病毒已引起重大流行,并通过埃及伊蚊和/或白纹伊蚊传播。 “ Sementis哥本哈根载体”(SCV)系统是最近开发的基于牛痘,繁殖缺陷的疫苗载体技术,可在修饰的CHO细胞中生产。在这里,我们描述了一种单载体构建SCV疫苗,该疫苗编码来自不同基因座的寨卡病毒和基孔肯雅病毒的结构多蛋白盒。小鼠的单次疫苗接种可在野生型和IFNAR -/-小鼠中诱导针对两种病毒的中和抗体,并可预防(i)野生型小鼠的基孔肯雅病毒毒血症和关节炎,(ii)寨卡病毒雌性IFNAR -/-小鼠的病毒血症和胎儿/胎盘感染,以及(iii)雄性IFNAR -/-小鼠的寨卡病毒病毒血症和睾丸感染以及病理。据我们所知,这代表了第一个单载体构建物,编码大蛋白的多病原体疫苗,为这些经常同时流行的虫媒病毒提供了简化的制造和配方,并减轻了“注射负担”。

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