Durbin Anna P, McArthur Julie, Marron Jennifer A, Blaney Joseph E, Thumar Bhavin, Wanionek Kim, Murphy Brian R, Whitehead Stephen S
Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Hum Vaccin. 2006 Jul-Aug;2(4):167-73. doi: 10.4161/hv.2.4.2944. Epub 2006 Jul 24.
The live attenuated DEN1 vaccine candidate virus rDEN1Delta30 has been evaluated in preclinical animal models and found to be attenuated and immunogenic. These promising preclinical studies have identified rDEN1Delta30 as a candidate DEN1 vaccine virus for further testing in a human Phase I clinical trial.
rDEN1Delta30 at a dose of 10(3) pfu was administered as a single inoculation to twenty healthy adult volunteers. Eight additional volunteers received placebo. Volunteers were monitored closely for adverse events and serum was collected on study days 0, 28, 42 and 180 for determination of neutralizing antibody titer.
The vaccine was well tolerated by the vaccinees. The most common adverse events observed were a transient asymptomatic rash in 40% of vaccinees and a mild neutropenia in 45% of vaccinees. No vaccinee developed a dengue-like illness. The vaccine was highly infectious and immunogenic with 95% of vaccinees developing a > or =4-fold rise in serum neutralizing antibody titer against DEN1 that persisted throughout the six month duration of the trial.
The rDEN1Delta30 vaccine is safe and induced a potent and durable antibody response against DEN1. It is a promising vaccine candidate for inclusion in a tetravalent dengue vaccine formulation.
减毒活登革病毒1型候选疫苗rDEN1Delta30已在临床前动物模型中进行评估，发现其具有减毒和免疫原性。这些有前景的临床前研究已将rDEN1Delta30确定为一种候选登革病毒1型疫苗病毒，用于在人类I期临床试验中进行进一步测试。
将剂量为10(3) 蚀斑形成单位（pfu）的rDEN1Delta30作为单次接种给予20名健康成年志愿者。另外8名志愿者接受安慰剂。密切监测志愿者的不良事件，并在研究第0、28、42和180天收集血清，以测定中和抗体滴度。
疫苗接种者对该疫苗耐受性良好。观察到的最常见不良事件是40%的接种者出现短暂无症状皮疹，45%的接种者出现轻度中性粒细胞减少。没有接种者出现登革热样疾病。该疫苗具有高度传染性和免疫原性，95%的接种者针对登革病毒1型的血清中和抗体滴度升高≥4倍，且在整个六个月的试验期间持续存在。
rDEN1Delta30疫苗安全，并诱导了针对登革病毒1型的强效且持久的抗体反应。它是一种有前景的候选疫苗，可纳入四价登革疫苗配方。
