Department of International Health, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0412, Japan.
Microbes Infect. 2011 Nov;13(12-13):1091-8. doi: 10.1016/j.micinf.2011.06.008. Epub 2011 Jul 1.
Most dengue vaccines currently under development are designed to induce neutralizing antibodies. Although neutralizing antibodies are believed to be protective, most of the antibody species that have neutralizing activities also have infection-enhancing activities at subneutralizing doses. Thus, the balance of neutralizing and enhancing activities induced by a dengue tetravalent vaccine was analyzed in this study in a DNA vaccine model using mice. The balance was measured using semi-adherent K562 cells in an assay system we previously developed. This system detected enhancing activities in sera from mice immunized with the vaccine when complement was absent from the virus-antibody mixture in this assay. Mice passively transferred with vaccinated mouse sera or monoclonal antibodies that possessed neutralizing activities as determined on Vero cells, also showed enhancing activities in their sera during the course of antibody waning in the absence of complement. However, these enhancing activities were abolished or altered to neutralizing activities in the presence of complement in our assay system, except in mice passively transferred with a monoclonal antibody of isotype IgG1. Thus, enhancing activities were not shown in mice immunized with a DNA vaccine as far as complement was included in our in vitro assay system.
大多数正在开发的登革热疫苗旨在诱导中和抗体。虽然中和抗体被认为是具有保护作用的，但大多数具有中和活性的抗体种类在亚中和剂量下也具有感染增强活性。因此，本研究在使用小鼠的 DNA 疫苗模型中分析了四价登革热疫苗诱导的中和和增强活性的平衡。该平衡使用我们之前开发的半贴壁 K562 细胞测定系统进行测量。该系统在检测血清中的增强活性时，在该测定中，当补体不存在于病毒-抗体混合物中时，来自用疫苗免疫的小鼠的血清中存在增强活性。在缺乏补体的情况下，在抗体衰减过程中，被动转移用接种过的小鼠血清或在 Vero 细胞上具有中和活性的单克隆抗体的小鼠，其血清中也显示出增强活性。然而，在我们的测定系统中，除了被动转移 IgG1 同种型单克隆抗体的小鼠外，这些增强活性在补体存在下被消除或转变为中和活性。因此，只要我们的体外测定系统中包含补体，用 DNA 疫苗免疫的小鼠就不会显示出增强活性。
