Borja-Tabora Charissa, Fernando LakKumar, Lopez Medina Eduardo, Reynales Humberto, Rivera Luis, Saez-Llorens Xavier, Sirivichayakul Chukiat, Yu Delia, Folschweiller Nicolas, Moss Kelley J, Rauscher Martina, Tricou Vianney, Zhao Yuan, Biswal Shibadas
Clinical Research Division, Research Institute for Tropical Medicine, Muntinlupa, Philippines.
Centre for Clinical Management of Dengue & Dengue Haemorrhagic Fever, Negombo General Hospital, Negombo, Sri Lanka.
Clin Infect Dis. 2025 Feb 5;80(1):199-206. doi: 10.1093/cid/ciae369.
Dengue is an increasing threat to global health. This exploratory analysis evaluated the immunogenicity, safety, and vaccine efficacy (VE) of a live-attenuated tetravalent dengue vaccine (TAK-003) in participants enrolled in the phase 3 DEN-301 trial (NCT02747927), stratified by baseline age (4-5 years, 6-11 years, or 12-16 years).
Participants were randomized 2:1 to receive 2 doses of TAK-003, administered 3 months apart, or placebo. Dengue serostatus was evaluated at enrolment. VE against virologically confirmed dengue (VCD) and hospitalized VCD; immunogenicity (geometric mean titers [GMTs]); and safety were evaluated per age group through ∼4 years postvaccination.
VE against VCD across serotypes was 43.5% (95% confidence interval [CI]: 25.3%, 57.3%) for 4-5 year-olds; 63.5% (95% CI: 56.9%, 69.1%) for 6-11 year-olds, and 67.7% (95% CI: 57.8%, 75.2%) for 12-16 year-olds. VE against hospitalized VCD was 63.8% (95% CI: 21.1%, 83.4%), 85.1% (95% CI: 77.1%, 90.3%), and 89.7% (95% CI: 77.9%, 95.2%), for the 3 age groups, respectively. GMTs remained elevated against all 4 serotypes for ∼4 years postvaccination, with no evident differences across age groups. No clear differences in safety by age were identified.
This exploratory analysis shows TAK-003 was efficacious in dengue prevention across age groups in children and adolescents 4-16 years of age living in dengue endemic areas. Relatively lower VE in 4-5 year-olds was potentially confounded by causative serotype distribution, small sample size, and VE by serotype, and should be considered in benefit-risk evaluations in this age group.
登革热对全球健康构成的威胁日益增加。本探索性分析评估了在3期DEN - 301试验（NCT02747927）中入组的参与者中，一种减毒活四价登革热疫苗（TAK - 003）的免疫原性、安全性和疫苗效力（VE），并按基线年龄（4 - 5岁、6 - 11岁或12 - 16岁）进行分层。
参与者按2:1随机分组，分别接受间隔3个月接种的2剂TAK - 003或安慰剂。在入组时评估登革热血清状态。通过疫苗接种后约4年，按年龄组评估针对病毒学确诊登革热（VCD）和住院VCD的VE、免疫原性（几何平均滴度[GMTs]）以及安全性。
4 - 5岁儿童针对各血清型VCD的VE为43.5%（95%置信区间[CI]：25.3%，57.3%）；6 - 11岁儿童为63.5%（95%CI：56.9%，69.1%）；12 - 16岁青少年为67.7%（95%CI：57.8%，75.2%）。针对住院VCD的VE在这三个年龄组中分别为63.8%（95%CI：21.1%，83.4%）、85.1%（95%CI：77.1%，90.3%）和89.7%（95%CI：77.9%，95.2%）。疫苗接种后约4年，针对所有4种血清型的GMTs仍保持升高，各年龄组之间无明显差异。未发现年龄对安全性有明显差异。
本探索性分析表明，TAK - 003对生活在登革热流行地区的4 - 16岁儿童和青少年各年龄组预防登革热有效。4 - 5岁儿童相对较低的VE可能受到致病血清型分布、样本量小以及各血清型VE的影响，在该年龄组的获益 - 风险评估中应予以考虑。
