Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910, USA.
Virology. 2010 Jan 20;396(2):280-8. doi: 10.1016/j.virol.2009.10.023. Epub 2009 Nov 13.
A new vaccination strategy for dengue virus (DENV) was evaluated in rhesus macaques by priming with tetravalent purified inactivated virus (TPIV) or tetravalent plasmid DNA vaccines expressing the structural prME gene region (TDNA) then boosting 2 months later with a tetravalent live attenuated virus (TLAV) vaccine. Both vaccine combinations elicited virus neutralizing (N) antibodies. The TPIV/TLAV combination afforded complete protection against DENV 3 challenge at month 8. In a second experiment, priming with TPIV elicited N antibodies against all four serotypes (GMT 1:28 to 1:43). Boosting with TLAV led to an increase in the GMT for each serotype (1:500 to 1:1200 for DENVs 1, 3, and 4, and greater than 1:6000 for DENV 2), which declined by month 8 (GMT 1:62 for DENV 3, 1:154 for DENV 1, 1:174 for DENV 4, and 1:767 for DENV 2). After challenge with each one of the four DENV serotypes, vaccinated animals exhibited no viremia but showed anamnestic antibody responses to the challenge viruses.
一种新的登革热病毒（DENV）疫苗接种策略在恒河猴中进行了评估，方法是用四价纯化灭活病毒（TPIV）或表达结构蛋白前体 ME 基因区（TDNA）的四价质粒 DNA 疫苗进行初免，然后在两个月后用四价减毒活疫苗（TLAV）进行加强。两种疫苗组合都能诱导产生病毒中和（N）抗体。TPIV/TLAV 组合在第 8 个月时完全能预防 DENV3 型的挑战。在第二项实验中，用 TPIV 初免可诱导针对所有 4 种血清型的 N 抗体（GMT 为 1:28 至 1:43）。用 TLAV 加强后，每种血清型的 GMT 都有所增加（DENV1、3 和 4 的 GMT 为 1:500 至 1:1200，DENV2 的 GMT 大于 1:6000），到第 8 个月时下降（DENV3 的 GMT 为 1:62，DENV1 的 GMT 为 1:154，DENV4 的 GMT 为 1:174，DENV2 的 GMT 为 1:767）。在接受四种 DENV 血清型中的每一种的挑战后，接种疫苗的动物没有病毒血症，但对挑战病毒表现出回忆性抗体反应。
