医学
血清状态
登革热
接种疫苗
登革热疫苗
安慰剂
不利影响
疫苗效力
临床终点
置信区间
内科学
临床试验
免疫学
登革热病毒
病毒载量
人类免疫缺陷病毒(HIV)
替代医学
病理
作者
Esper G. Kallás,Murilo Bicudo Cintra,José A. Moreira,Elizabeth González Patiño,Patrícia Emília Braga,Jorge Tenorio,Vanessa Infante,Ricardo Palácios,Marcus Vinícius Guimarães Lacerda,Dhélio Batista Pereira,Allex Jardim da Fonseca,Ricardo Queiróz Gurgel,Ivo Castelo Branco Coêlho,Cor Jésus Fernandes Fontes,Ernesto T. A. Marques,Gustavo Romero,Mauro Martins Teixeira,André Machado Siqueira,Aldina Barral,Viviane Boaventura,Fabiano Ramos,Erivaldo Elias Júnior,José Cássio de Moraes,Dimas Tadeu Covas,Jorge Kalil,Alexander Roberto Precioso,Stephen S. Whitehead,Alejandra Esteves-Jaramillo,Tulin Shekar,Jungjin Lee,Jeannette Macey,Sabrina Gozlan Kelner,Beth-Ann Coller,Fernanda Castro Boulos,Maurício Lacerda Nogueira
标识
DOI:10.1056/nejmoa2301790
摘要
Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed.In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed.Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%).A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).