rDEN4Δ30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers
rDEN4Δ30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers
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DOI：
10.1086/427780
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发表时间：
2005-03-01
影响因子：
6.4
通讯作者：
Karron, RA
中科院分区：
文献类型：
--
作者：
Durbin, AP;Whitehead, SS;Karron, RA
背景资料。登革病毒4型(DEN-4)减毒活疫苗候选病毒rDEN4Delta30在10(5)个空斑形成单位(PFU)剂量下被发现是安全的和免疫原性。在一项后续的安慰剂对照的第二阶段临床试验中，rDEN4Delta30作为单次接种被给予3个单独的剂量队列(10(3)pfu、10(2)pfu或10(1)pfu)，以供进一步评估。每个剂量队列包括20名疫苗接种者和4名安慰剂接受者。对受试者进行严密的不良事件监测，并在研究的第28天和第42天采集血清进行中和抗体滴度测定。该疫苗在研究的所有剂量下都具有良好的耐受性。观察到的最常见的副作用是50%的接种者出现一过性无症状皮疹，20%的接种者出现轻度中性粒细胞减少。没有接种疫苗的人患上类似登革热的疾病。该疫苗具有高度的传染性和免疫原性，在每个剂量队列中，95%-100%的接种者血清中和抗体滴度增加了4倍以上。RDEN4Delta30疫苗是安全的，并诱导了一种抗体反应，这种抗体反应对基因多样性的DEN-4病毒具有广泛的中和作用。它是包含在四价登革热疫苗配方中的一个有希望的候选疫苗。
Background. The live attenuated dengue virus type 4 (DEN-4) vaccine candidate virus rDEN4Delta30 was previously found to be safe and immunogenic at a dose of 10(5) plaque-forming units (pfu).Methods. In a follow-up placebo-controlled phase 2 clinical trial, rDEN4Delta30 was administered as a single inoculation to 3 separate dose cohorts (10(3) pfu, 10(2) pfu, or 10(1) pfu), for further evaluation. Each dose cohort consisted of 20 vaccinees and 4 placebo recipients. Volunteers were monitored closely for adverse events, and serum was collected on study days 28 and 42 for determination of neutralizing antibody titer.Results. The vaccine was well tolerated at all doses studied. The most common adverse events observed were a transient asymptomatic rash in >50% of vaccinees and a mild neutropenia in similar to20% of vaccinees. No vaccinee developed a dengue-like illness. The vaccine was highly infectious and immunogenic, with 95%-100% of vaccinees in each dose cohort developing a greater than or equal to4-fold increase in titers of serum neutralizing antibodies against DEN-4.Conclusions. The rDEN4Delta30 vaccine is safe and induced an antibody response that was broadly neutralizing against genotypically diverse DEN-4 viruses. It is a promising vaccine candidate for inclusion in a tetravalent dengue vaccine formulation.