Phase 2 clinical trial of three formulations of tetravalent live-attenuated dengue vaccine in flavivirus-naive adults
Phase 2 clinical trial of three formulations of tetravalent live-attenuated dengue vaccine in flavivirus-naive adults
复制标题
DOI：
10.4161/hv.5.1.6348
复制
发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Edelman, Robert
中科院分区：
文献类型：
--
作者：
Sun, Wellington;Cunningham, Dennis;Edelman, Robert
我们的活减毒四价登革病毒疫苗（TDV）的16个剂量制剂的安全性和免疫原性先前进行了评估。选择十六种候选TDV制剂中的两种（制剂13和14）用于进一步评价。开发了一种新的TDV制剂，制剂17，其使用较高原代狗肾（PDK）细胞传代的登革-1病毒（DENV-1）和较低PDK细胞传代的DENV-4，以优化中和抗体应答。所有三种制剂均由10 exp 3 -5 pfu/剂量的四种登革热疫苗病毒血清型的组合组成。这项在71名健康成人受试者中进行的双盲、随机试验评价了疫苗的安全性、反应原性和免疫原性。在第0天和第180天（6个月）在三角肌中皮下给予TDV。受试者在研究第0、10、28、180、190和208天就诊，并在每次接种后填写每日症状日记，持续21天。制剂13的反应原性最强，而制剂14和17在报告的反应方面相似。分别有75%、31%和31%的受试者在初次接种制剂13、14和17后第10天出现病毒血症。接种第二剂疫苗后，任何受试者均未检测到病毒血症。免疫原性终点为第二次接种后1个月的中和抗体滴度。在两剂制剂13、14和17后，分别有36%、40%和63%的接种受试者产生四价中和抗体。基于该研究，选择制剂17用于进一步临床评价。
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.