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四价登革热疫苗对4-16岁健康儿童疗效显著
作者:小柯机器人 发布时间:2020/3/29 22:53:01

近日,位于美国的武田疫苗公司的Shibadas Biswal团队研究了四价登革热疫苗对4-16岁健康儿童的预防效果。2020年3月17日,《柳叶刀》杂志发表了这一成果。

安全有效的登革热疫苗仍供不应求,尤其是针对未感染登革热的人群和9岁以下儿童。

为了评估4-16岁健康儿童的减毒活四价登革热疫苗(TAK-003)的有效性、安全性和免疫原性,研究组在亚洲和拉丁美洲登革热流行地区进行了一项临床3期、随机、双盲实验,评估TAK-003疫苗接种后的效果。

2016年9月7日至2017年8月18日,研究组招募了20099名4-16岁的健康儿童,按2:1随机分组,分别接受两剂TAK-003或两剂安慰剂,间隔3个月。TAK-003的总体疫苗效力为80.2%。基线时血清阳性者的疫苗效力为76.1%,血清阴性者的疫苗效力为66.2%,针对住院登革热的效力为90.4%,针对登革热出血的效力为85.9%。

疫苗效力因个体血清型而异,其中DENV1为69.8%,DENV2为95.1%,DENV3为48.9%,DENV4为51.0%。TAK-003组严重不良事件累计率为4.0%,与安慰剂组相差不大(4.8%)。感染是导致严重不良事件的最常见原因。共有20名参与者因不良事件而退出试验,其中TAK-003组有14名,安慰剂组有6名。

总之,TAK-003对儿童症状性登革热具有良好的耐受性和免疫力,且与免疫前的血清状况无关,但疫苗效力因血清型而异。

附:英文原文

Title: Efficacy of a tetravalent dengue vaccine in healthy children aged 4–16 years: a randomised, placebo-controlled, phase 3 trial

Author: Shibadas Biswal, Charissa Borja-Tabora, Luis Martinez Vargas, Hector Velásquez, Maria Theresa Alera, Victor Sierra, Edith Johana Rodriguez-Arenales, Delia Yu, V Pujitha Wickramasinghe, Edson Duarte Moreira, Asvini D Fernando, Dulanie Gunasekera, Pope Kosalaraksa, Felix Espinoza, Eduardo López-Medina, Lulu Bravo, Suely Tuboi, Yanee Hutagalung, Pedro Garbes, Ian Escudero, Martina Rauscher, Svetlana Bizjajeva, Inge LeFevre, Astrid Borkowski, Xavier Saez-Llorens, Derek Wallace, Alys Concepción, Ana Cecilia Villarreal, Asvini Fernando, Charissa Borja-Tabora, Chukiat Sirivichayakul, Delia Yu, Dulanie Gunasekera, Eduardo López-Medina, Edith Johanna Rodriguez-Arenales, Edson Duarte Moreira Jr, Felix Espinoza, Hector Velásquez, Humberto Reynales, Kleber Luz, Jose Jimeno, LakKumar Fernando, Lulu Bravo, Luis Martinez Vargas, Luis Rivera, Maria Theresa Alera, Onanong Manacharoen, Pio Lopez, Pope Kosalaraksa, V. Pujitha Wickramasinghe, Reynaldo Dietze, Rivaldo Venancio da Cunha, Veerachai Watanaveeradej, Victor Sierra, Xavier Saez-Llorens, Shibadas Biswal, Manja Brose, Martina Rauscher, Svetlana Bizjajeva, Inge LeFevre, Astrid Borkowski, Derek Wallace, Ian Escudero, Kelley Moss, Pedro Garbes, Seetha Meyer, Yanee Hutagalung, Suely Tuboi, Vianney Tricou

Issue&Volume: 2020-03-17

Abstract: BackgroundA substantial unmet need remains for safe and effective vaccines against dengue virus disease, particularly for individuals who are dengue-naive and those younger than 9 years. We aimed to assess the efficacy, safety, and immunogenicity of a live attenuated tetravalent dengue vaccine (TAK-003) in healthy children aged 4–16 years.MethodsWe present data up to 18 months post-vaccination from an ongoing phase 3, randomised, double-blind trial of TAK-003 in endemic regions of Asia and Latin America (26 medical and research centres across Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). Healthy children aged 4–16 years were randomly assigned 2:1 (stratified by age and region) to receive two doses of TAK-003 or two doses of placebo, 3 months apart. Investigators, participants and their parents or guardians, and sponsor representatives advising on trial conduct were masked to trial group assignments. Participants presenting with febrile illness were tested for virologically confirmed dengue (VCD) by serotype-specific RT-PCR. In timeframes beginning 30 days post-second dose, the primary endpoint (overall vaccine efficacy) was assessed in the first 11 months, and the secondary endpoints (efficacy by baseline serostatus, serotype, hospitalised dengue, and severe dengue) in the first 17 months. This study is registered with ClinicalTrials.gov, NCT02747927.Findings20099 participants were randomly assigned and vaccinated between Sept 7, 2016, and Aug 18, 2017; 19021 (94·6%) were included in the per protocol analysis, and 20071 (99·9%) in the safety set. The primary endpoint was achieved with an overall vaccine efficacy of 80·2% (95% CI 73·3 to 85·3; 61 cases of VCD in the TAK-003 group vs 149 cases of VCD in the placebo group). In the secondary endpoint assessment timeframe, an overall vaccine efficacy of 73·3% (95% CI 66·5 to 78·8) was observed. Analysis of secondary endpoints showed efficacies of 76·1% (95% CI 68·5 to 81·9) in individuals who were seropositive at baseline, 66·2% (49·1 to 77·5) in individuals who were seronegative at baseline, 90·4% (82·6 to 94·7) against hospitalised dengue, and 85·9% (31·9 to 97·1) against dengue haemorrhagic fever. Efficacy varied by individual serotypes (DENV 1, 69·8% [95% CI 54·8 to 79·9]; DENV 2, 95·1% [89·9 to 97·6]; DENV 3, 48·9% [27·2 to 64·1]; DENV 4, 51·0% [–69·4 to 85·8]). Cumulative rates of serious adverse events were similar in TAK-003 (4·0%) and placebo (4·8%) recipients, and were consistent with expected medical disorders in the study population. Infection was the most frequent reason leading to serious adverse events. 20 participants (<0·1% of the safety set) were withdrawn from the trial due to 21 adverse events by the end of part two; 14 of these participants received TAK-003 and six received placebo.InterpretationTAK-003 was well tolerated and efficacious against symptomatic dengue in children regardless of serostatus before immunisation. Vaccine efficacy varied by serotype, warranting continued follow-up to assess longer-term vaccine performance.

DOI: 10.1016/S0140-6736(20)30414-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30414-1/fulltext

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
官方网址:http://www.thelancet.com/
投稿链接:http://ees.elsevier.com/thelancet