A tetravalent recombinant dengue domain III protein vaccine stimulates neutralizing and enhancing antibodies in mice
A tetravalent recombinant dengue domain III protein vaccine stimulates neutralizing and enhancing antibodies in mice
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DOI：
10.1016/j.vaccine.2010.10.004
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发表时间：
2010-11-29
期刊：
影响因子：
5.5
通讯作者：
Schlesinger, Jacob J.
中科院分区：
文献类型：
--
作者：
Block, Olivia K. T.;Rodrigo, W. W. Shanaka I.;Schlesinger, Jacob J.
登革热病毒作为四种不同的血清学病毒(DENV1-4)共同传播，通常按顺序感染个体。目前的DENV候选疫苗整合了整个病毒包膜E蛋白(E)胞外区，从而刺激了DENV血清型特异性抗体和交叉反应抗体。因为后者可能会增加自然获得性感染，所以这种疫苗配方必须是四价的。我们评估了对E结构域III(DIII)蛋白的中和和增强抗体反应，其中血清特异性中和决定簇集中在E结构域III蛋白中。用昆虫细胞分泌的重组DENV-DIII蛋白单独免疫并以四价组合免疫的小鼠，产生了血清特异性的IgG1中和抗体，但在Fc-Gamma R细胞中仍显示出可测量的DENV增强活性。针对DENV-DIII靶向中和抗体生产的疫苗策略仍然具有吸引力，但可能需要进一步修改以诱导安全的保护性免疫。(C)2010爱思唯尔有限公司。保留所有权利。
Dengue viruses co-circulate as four serologically distinct viruses (DENV1-4) that commonly infect individuals sequentially. Current DENV candidate vaccines incorporate the entire virion envelope E protein (E) ectodomain thereby stimulating both DENV serotype-specific and cross-reactive antibodies. Because the latter may enhance naturally acquired infection, such vaccine formulations must be tetravalent. We evaluated the neutralizing and enhancing antibody response to E domain III (dIII) proteins, in which serotype-specific neutralizing determinants are concentrated. Mice immunized with insect cell-secreted recombinant DENV-dIII proteins individually, and in tetravalent combination, produced serotype-specific IgG1 neutralizing antibodies that nevertheless exhibited measurable DENV enhancing activity in Fc gamma R-bearing cells. Vaccine strategies directed to DENV-dIII-targeted neutralizing antibody production remain attractive but will likely require further modifications to induce safe, protective immunity. (c) 2010 Elsevier Ltd. All rights reserved.