Simasathien Sriluck, Thomas Stephen J, Watanaveeradej Veerachai, Nisalak Ananda, Barberousse Célia, Innis Bruce L, Sun Wellington, Putnak J Robert, Eckels Kenneth H, Hutagalung Yanee, Gibbons Robert V, Zhang Chunlin, De La Barrera Rafael, Jarman Richard G, Chawachalasai Wipa, Mammen Mammen P
Department of Pediatrics, Phramongkutklao Hospital, Bangkok, Thailand.
Am J Trop Med Hyg. 2008 Mar;78(3):426-33.
A live-attenuated tetravalent dengue virus (DENV) vaccine candidate has been well tolerated and immunogenic in healthy, US flavivirus naive adult volunteers. We conducted a pilot, safety, and immunogenicity trial of the vaccine candidate in healthy Thai children (6-7 years of age) to prepare for its eventual evaluation in Thai infants. In an uncontrolled, open clinical trial, the investigational vaccine was administered on study Days 0 and 180 to seven volunteers residing in Bangkok without neutralizing antibodies to DENV1-4 or to Japanese encephalitis virus (JEV). Clinical and laboratory safety assessments were completed during the 30 days after each vaccine dose, and immunogenicity was determined at Day 30. In this study, the vaccine was well tolerated with no serious adverse events or alert laboratory values. One volunteer experienced fever (38.2 degrees C, < 2 days) and associated DENV4 vaccine viremia 7 days after Dose 2. One month after Dose 2, six volunteers in the per-protocol analysis exhibited a tetravalent neutralizing antibody response with DENV1-4 geometric mean titers of 55, 475, 350, and 171, respectively. Ten weeks (~75 days) after Dose 2, five of the six volunteers continued to exhibit a tetravalent neutralizing antibody profile; one volunteer's DENV4 PRNT50 titer fell below the assay cut-off (29 --> < 10); (clinicaltrials.gov NCT00384670).
一种减毒活四价登革病毒（DENV）候选疫苗在健康、未感染过黄病毒的美国成年志愿者中耐受性良好且具有免疫原性。我们在健康的泰国儿童（6 - 7岁）中开展了该候选疫苗的初步安全性和免疫原性试验，为其最终在泰国婴儿中的评估做准备。在一项非对照、开放性临床试验中，研究用疫苗于研究第0天和第180天给予居住在曼谷的7名对DENV1 - 4及日本脑炎病毒（JEV）无中和抗体的志愿者。每次疫苗接种后30天内完成临床和实验室安全性评估，并在第30天测定免疫原性。在本研究中，该疫苗耐受性良好，未出现严重不良事件或警示性实验室指标。一名志愿者在第2剂接种后7天出现发热（38.2摄氏度，持续<2天）及相关的DENV4疫苗病毒血症。在第2剂接种后1个月，符合方案分析中的6名志愿者呈现四价中和抗体反应，DENV1 - 4的几何平均滴度分别为55、475、350和171。在第2剂接种后10周（约75天），6名志愿者中的5名继续呈现四价中和抗体谱；一名志愿者的DENV4 PRNT50滴度降至检测下限以下（29 --> <10）；（clinicaltrials.gov NCT00384670）
