El Hindi Tarek, Alera Maria Theresa, Bravo Lulu, Moreira Edson Duarte, Dietze Reynaldo, Oliveira Ana Lucia, Watanaveeradej Veerachai, Zhao Yuan, Sonderegger Ivo, Tricou Vianney, Folschweiller Nicolas, Biswal Shibadas
Vaccines Business Unit, Takeda Pharmaceuticals International AG, Zurich, Switzerland.
Virology Research Unit, Philippines-Armed Forces Research Institute of Medical Sciences, Cebu City.
J Infect Dis. 2025 Jul 11;231(6):e1160-e1169. doi: 10.1093/infdis/jiaf145.
TAK-003 has been shown to be well tolerated and effective against symptomatic dengue disease and hospitalization, irrespective of baseline serostatus. Most infections are asymptomatic/subclinical. This study assessed whether TAK-003 could protect against asymptomatic/subclinical infections by evaluating increased neutralizing antibody (NAb) titers after natural infection.
DEN-301 (NCT02747927) is a phase 3 trial among 4- to 16-year-old participants who received 2 doses of TAK-003 or placebo 3 months apart. These exploratory analyses used NAb measured during the trial. As no well-accepted definition for asymptomatic infection exists, 3 algorithms were evaluated: (1) 4-fold increase in NAb, (2) 4-fold increase in NAb and a minimum titer of 40, and (3) 4-fold increase in NAb and a minimum titer of 4-fold lower limit of quantification. Months 4 to 9, months 9 to 15, and months 15 to 27 after first vaccination were analyzed.
NAbs from 3765 participants were analyzed. From months 4 to 9, vaccine efficacy (VE) against asymptomatic infection was 51.1% (95% CI, 30.4%-65.6%), 36.1% (95% CI, 6.7%-56.3%), and 27.3% (95% CI, -8.2% to 51.2%) for algorithms 1, 2, and 3, respectively. VE per algorithms 1, 2, and 3 was 54.8% (95% CI, 28.8%-71.3%), 47.9% (95% CI, 16.8%-67.4%), and 44.3% (95% CI, 9.9%-65.6%) in participants with baseline seropositivity and 44.4% (95% CI, 2.1%-68.4%), 4.6% (95% CI, -85.1% to 50.8%), and -29.3% (95% CI, -172.1% to 38.6%) in those with baseline seronegativity. VE against asymptomatic infection gradually decreased from months 4 to 9 to months 9 to 15 and from months 9 to 15 to months 15 to 27.
The variability in VE algorithms indicates challenges in accurately assessing VE against asymptomatic infections. TAK-003 had a modest impact on asymptomatic dengue infections in the first months postvaccination, mainly in participants with baseline seropositivity.
TAK-003已被证明耐受性良好，对有症状的登革热疾病和住院治疗有效，无论基线血清状态如何。大多数感染是无症状/亚临床的。本研究通过评估自然感染后中和抗体（NAb）滴度的增加，来评估TAK-003是否能预防无症状/亚临床感染。
DEN-301（NCT02747927）是一项针对4至16岁参与者的3期试验，他们每隔3个月接受2剂TAK-003或安慰剂。这些探索性分析使用了试验期间测量的NAb。由于不存在被广泛接受的无症状感染定义，评估了3种算法：（1）NAb增加4倍，（2）NAb增加4倍且最低滴度为40，（3）NAb增加4倍且最低滴度为定量下限的4倍。分析了首次接种疫苗后第4至9个月、第9至15个月和第15至27个月的数据。
分析了3765名参与者的NAb。在第4至9个月，算法1、2和3针对无症状感染的疫苗效力（VE）分别为51.1%（95%CI，30.4%-65.6%）、36.1%（95%CI，6.7%-56.3%）和27.3%（95%CI，-8.2%至51.2%）。算法1、2和3在基线血清阳性参与者中的VE分别为54.8%（95%CI，28.8%-71.3%）、47.9%（95%CI，16.8%-67.4%）和44.3%（95%CI，9.9%-65.6%）；在基线血清阴性参与者中的VE分别为44.4%（95%CI，2.1%-68.4%）、4.6%（95%CI，-85.1%至50.8%）和-29.3%（95%CI，-172.1%至38.6%）。针对无症状感染的VE从第4至9个月到第9至15个月以及从第9至15个月到第15至27个月逐渐下降。
VE算法的变异性表明在准确评估针对无症状感染的VE方面存在挑战。TAK-003在疫苗接种后的头几个月对无症状登革热感染有一定影响，主要是在基线血清阳性的参与者中。
