Hospital Maternidad Nuestra Senora de Altagracia, Santo Domingo, Dominican Republic.
Takeda Vaccines, Inc., Boston, Massachusetts, USA.
Clin Infect Dis. 2022 Aug 24;75(1):107-117. doi: 10.1093/cid/ciab864.
Takeda's live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across 8 dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year postvaccination. This exploratory analysis provides an update with cumulative and third-year data.
Healthy 4-16 year olds (n = 20099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific reverse transcriptase-polymerase chain reaction.
Cumulative efficacy after 3 years was 62.0% (95% confidence interval, 56.6-66.7) against virologically confirmed dengue (VCD) and 83.6% (76.8-88.4) against hospitalized VCD. Efficacy was 54.3% (41.9-64.1) against VCD and 77.1% (58.6-87.3) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9-70.1) against VCD and 86.0% (78.4-91.0) against hospitalized VCD in baseline seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5-54.7), whereas efficacy against hospitalized VCD was sustained at 70.8% (49.6-83.0). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (ie, second half of the 3 years following vaccination), but none were related. No important safety risks were identified.
TAK-003 was efficacious against symptomatic dengue over 3 years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.
武田的减毒活四价登革热候选疫苗（TAK-003）正在 8 个登革热流行国家进行长期临床试验评估。此前，我们已经报告了其在血清阴性和血清阳性参与者中的疗效和安全性，并且其表现因血清型而异，接种疫苗后第一至第二年的疗效有所下降。这项探索性分析提供了累积数据和第三年的数据更新。
健康的 4-16 岁儿童（n=20099）按 2:1 的比例随机分为 TAK-003 组或安慰剂组（0、3 个月方案）。该方案包括对所有参与者进行基线血清学检测，并在整个试验过程中使用血清型特异性逆转录聚合酶链反应检测所有症状性登革热。
接种疫苗后 3 年的累积疗效为 62.0%（95%置信区间，56.6-66.7），对病毒学确诊的登革热（VCD）有效，83.6%（76.8-88.4）对住院 VCD 有效。在基线血清阴性者中，对 VCD 的疗效为 54.3%（41.9-64.1），对住院 VCD 的疗效为 77.1%（58.6-87.3），在基线血清阳性者中，对 VCD 的疗效为 65.0%（58.9-70.1），对住院 VCD 的疗效为 86.0%（78.4-91.0）。第三年 VCD 的疗效下降至 44.7%（32.5-54.7），而住院 VCD 的疗效仍保持在 70.8%（49.6-83.0）。在正在进行的长期随访（即接种疫苗后第三年的下半年）中，TAK-003 组的严重不良事件发生率为 2.9%，安慰剂组为 3.5%，但均与疫苗无关。未发现重要的安全风险。
TAK-003 在 3 年期间对有症状的登革热有效。疗效随时间下降，但对住院登革热仍保持强劲。计划进行加强剂量评估。
