Sun Wellington, Cunningham Dennis, Wasserman Steven S, Perry Judith, Putnak J Robert, Eckels Kenneth H, Vaughn David W, Thomas Stephen J, Kanesa-Thasan Niranjan, Innis Bruce L, Edelman Robert
Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Hum Vaccin. 2009 Jan-Feb;5(1):33-40. doi: 10.4161/hv.5.1.6348. Epub 2009 Jan 27.
Sixteen dose formulations of our live-attenuated tetravalent dengue virus vaccines (TDV) were previously evaluated for safety and immunogenicity. Two of the sixteen candidate TDV formulations (Formulations 13 and 14) were selected for further evaluation. A new TDV formulation, Formulation 17, using a higher primary dog kidney (PDK) cell passage Dengue-1 virus (DENV-1) and a lower PDK cell passage DENV-4, was developed to optimize the neutralizing antibody response. All three formulations consist of combinations of 10exp3-5 pfu/dose of the four dengue vaccine virus serotypes. This double-blind, randomized trial in 71 healthy adult subjects evaluated vaccine safety, reactogenicity and immunogenicity. TDV's were given subcutaneously in the deltoid on Day 0 and 180 (6 months). Subjects were seen in clinic on Study Days 0, 10, 28, 180, 190 and 208 and filled out daily symptom diaries for 21 days after each vaccination. Formulation 13 was the most reactogenic, while both Formulations 14 and 17 were similar in reported reactions. Seventy-five percent, 31% and 31% of subjects were viremic on Day 10 after primary vaccination with Formulations 13, 14 and 17 respectively. Viremia was not detected in any subject following the second dose of vaccine. The immunogenicity endpoint was neutralizing antibody titer one month after the second vaccination. Thirty-six percent, 40% and 63% of vaccinated subjects developed tetravalent neutralizing antibodies after two doses of Formulations 13, 14 and 17, respectively. Formulation 17 was selected for further clinical evaluation based on this study.
我们之前对十六种剂量配方的减毒活四价登革病毒疫苗（TDV）进行了安全性和免疫原性评估。从这十六种候选TDV配方中挑选出两种（配方13和14）进行进一步评估。研发了一种新的TDV配方，即配方17，它使用了更高代次的原代犬肾（PDK）细胞传代的登革1型病毒（DENV-1）和更低代次的PDK细胞传代的DENV-4，以优化中和抗体反应。所有三种配方均由四种登革疫苗病毒血清型按10exp3 - 5 pfu/剂量组合而成。这项针对71名健康成年受试者的双盲、随机试验评估了疫苗的安全性、反应原性和免疫原性。TDV于第0天和第180天（6个月）在三角肌皮下注射。在研究第0、10、28、180、190和208天对受试者进行临床观察，并在每次接种疫苗后21天填写每日症状日记。配方13的反应原性最强，而配方14和17报告的反应相似。分别用配方13、14和17进行初次接种后，第10天有75%、31%和31%的受试者出现病毒血症。第二次接种疫苗后，未在任何受试者中检测到病毒血症。免疫原性终点是第二次接种疫苗后一个月的中和抗体滴度。分别接种两剂配方13、14和17后，36%、40%和63%的接种受试者产生了四价中和抗体。基于这项研究，选择配方17进行进一步的临床评估。
