Lazo Laura, Hermida Lisset, Zulueta Aída, Sánchez Jorge, López Carlos, Silva Ricardo, Guillén Gerardo, Guzmán María G
Centro de Ingeniería Genética y Biotecnología, Apdo 6162, Habana 10600, Cuba.
Vaccine. 2007 Jan 22;25(6):1064-70. doi: 10.1016/j.vaccine.2006.09.068. Epub 2006 Oct 9.
In the present work, we study the immunogenicity and protective capacity of a recombinant capsid protein from Dengue-2 virus. The capsid gene was cloned under the T5 phage promoter and expressed in Escherichia coli. The recombinant protein was obtained mainly associated to the soluble fraction upon cellular disruption and exhibited a pattern of high aggregation, determined by gel filtration chromatography. The semipurified preparation was inoculated in mice and after three doses, no antiviral antibodies were induced. On the other hand, mice intracranially challenged with homologous lethal virus, exhibited statistically significant protection with respect to the control group. These results describe, for the first time, the protective capacity of the capsid protein of Dengue virus indicating the existence of a protector mechanism, which is totally independent of the antibodies. This lack of induction of antiviral antibodies makes the capsid protein an attractive vaccine candidate against dengue since eliminates the potential risk of the induction of antibody dependent enhancement associated to the current vaccines under study.
在本研究中，我们研究了登革2型病毒重组衣壳蛋白的免疫原性和保护能力。衣壳基因在T5噬菌体启动子下克隆并在大肠杆菌中表达。重组蛋白在细胞破碎后主要存在于可溶性部分，并通过凝胶过滤色谱法确定其具有高度聚集的模式。将半纯化制剂接种到小鼠体内，三次给药后，未诱导出抗病毒抗体。另一方面，用同源致死病毒进行颅内攻击的小鼠相对于对照组表现出统计学上显著的保护作用。这些结果首次描述了登革病毒衣壳蛋白的保护能力，表明存在一种完全独立于抗体的保护机制。抗病毒抗体的缺乏使得衣壳蛋白成为一种有吸引力的抗登革热疫苗候选物，因为它消除了与目前正在研究的疫苗相关的抗体依赖性增强的潜在风险。
