Viral Genomics and Vaccination Unit, Institut Pasteur, CNRS-URA3015, 28 rue du Dr Roux, 75015 Paris, France.
Vaccine. 2010 Sep 24;28(41):6730-9. doi: 10.1016/j.vaccine.2010.07.073. Epub 2010 Aug 3.
Dengue disease is an increasing global health problem that threatens one-third of the world's population. To control this emerging arbovirus, an efficient preventive vaccine is still needed. Because four serotypes of dengue virus (DV) coexist and antibody-dependent enhanced infection may occur, most strategies developed so far rely on the administration of tetravalent formulations of four live attenuated or chimeric viruses. Here, we evaluated a new strategy based on the expression of a single minimal tetravalent DV antigen by a single replicating viral vector derived from pediatric live-attenuated measles vaccine (MV). We generated a recombinant MV vector expressing a DV construct composed of the four envelope domain III (EDIII) from the four DV serotypes fused with the ectodomain of the membrane protein (ectoM). After two injections in mice susceptible to MV infection, the recombinant vector induced neutralizing antibodies against the four serotypes of dengue virus. When immunized mice were further inoculated with live DV from each serotype, a strong memory neutralizing response was raised against all four serotypes. A combined measles-dengue vaccine might be attractive to immunize infants against both diseases where they co-exist.
登革热疾病是一个日益严重的全球健康问题，威胁着世界上三分之一的人口。为了控制这种新出现的虫媒病毒，仍然需要一种有效的预防疫苗。由于存在四种登革热病毒（DV）血清型，并且可能发生抗体依赖性增强感染，因此迄今为止大多数开发的策略都依赖于四种活减毒或嵌合病毒的四价制剂。在这里，我们评估了一种基于由源自小儿活减毒麻疹疫苗（MV）的单个复制病毒载体表达的单个最小四价 DV 抗原的新策略。我们生成了一种表达由四个 DV 血清型的四个包膜结构域 III（EDIII）与膜蛋白（ectoM）的外显子融合而成的 DV 构建体的重组 MV 载体。在易感染 MV 感染的小鼠中进行两次注射后，重组载体诱导了针对四种登革热病毒血清型的中和抗体。当用来自每个血清型的活 DV 免疫接种小鼠时，针对所有四种血清型都引发了强烈的记忆中和反应。一种联合的麻疹-登革热疫苗可能对同时存在这两种疾病的婴儿具有吸引力。
