From Instituto Butantan (E.G.K., M.A.T.C., J.A.M., E.G.P., P.E.B., J.C.V.T., V.I., R.P., D.T.C., J.K., A.R.P., F.C.B.), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (E.G.K.), Departamento de Saúde Coletiva, Faculdade de Ciências Médicas Santa Casa de São Paulo (J.C.M.), and Departamento de Clínica Médica, Faculdade de Medicina, Universidade de São Paulo (J.K.), São Paulo, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus (M.V.G.L.), Centro de Pesquisa em Medicina Tropical de Rôndonia, Porto Velho (D.B.P.), Universidade Federal de Roraima, Boa Vista (A.J.F.), Programa de Pós-graduação em Ciências da Saúde, Universidade Federal de Sergipe, Aracaju (R.Q.G.), Faculdade de Medicina da Universidade Federal do Ceará, Fortaleza (I.C.-B.C.), Hospital Universitário Júlio Müller, Cuiabá (C.J.F.F.), Institute Aggeu Magalhães, Fundação Oswaldo Cruz, Recife (E.T.A.M.), Núcleo de Medicina Tropical, Faculdade de Medicina, Universidade de Brasília, Brasília (G.A.S.R.), the Center for Advanced and Innovative Therapies, Universidade Federal de Minas Gerais, Belo Horizonte (M.M.T.), Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro (A.M.S.), Medicina e Saúde Pública de Precisão, Fundação Oswaldo Cruz-Instituto Gonçalo Moniz (IGM/FIOCRUZ), Salvador (A.M.P.B., V.S.B.), Hospital São Lucas da Pontificia Universidade Católica do Rio Grande do Sul, Porto Alegre (F.R.), Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul, Campo Grande (E.E.J.), Faculdade de Medicina de Ribeirão Preto, Universidade of São Paulo, Ribeirão Preto (D.T.C.), and Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto (M.L.N.) - all in Brazil; the School of Public Health, University of Pittsburgh, Pittsburgh (E.T.A.M.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (S.S.W.); Merck, Rahway, NJ (A.E.-J., T.S., J.-J.L., S.G.K., B.-A.G.C.); Merck Sharp and Dohme, Munro, Argentina (J.M.); and the Department of Pathology, University of Texas Medical Branch, Galveston (M.L.N.).
N Engl J Med. 2024 Feb 1;390(5):397-408. doi: 10.1056/NEJMoa2301790.
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.).
布坦坦登革热疫苗（布坦坦-DV）是一种正在研究中的、单剂量、减毒、四价疫苗，可预防登革热疾病，但需要提供其总体疗效数据。
在巴西进行的一项正在进行的 3 期、双盲试验中，我们将参与者随机分配接受布坦坦-DV 或安慰剂，按年龄分层（2 至 6 岁、7 至 17 岁和 18 至 59 岁）；计划进行 5 年的随访。试验的目的是评估针对任何血清型登革热的总体疫苗效力，这些登革热在接种后 28 天以上出现症状并经病毒学确认（主要疗效终点），无论基线时的血清状态如何，并描述直至第 21 天的安全性（主要安全性终点）。在这里，根据每个参与者 2 年的随访来评估疫苗效力，根据接种后 21 天内报告的与疫苗相关的不良事件来评估安全性。关键次要目标是根据基线时的登革热血清状态和登革热病毒血清型评估参与者中的疫苗效力；还评估了按年龄划分的疫苗效力。
在 3 年的招募期内，共有 16235 名参与者接受了布坦坦-DV（10259 名参与者）或安慰剂（5976 名参与者）。2 年的总体疫苗效力为 79.6%（95%置信区间[CI]，70.0 至 86.3）-73.6%（95%CI，57.6 至 83.7），在无登革热暴露史的参与者中为 89.2%（95%CI，77.6 至 95.6），在有暴露史的参与者中为 80.1%（95%CI，66.0 至 88.4）。2 至 6 岁的参与者疫苗效力为 80.1%（95%CI，66.0 至 88.4），7 至 17 岁的参与者为 77.8%（95%CI，55.6 至 89.6），18 至 59 岁的参与者为 90.0%（95%CI，68.2 至 97.5）。针对 DENV-1 的效力为 89.5%（95%CI，78.7 至 95.0），针对 DENV-2 的效力为 69.6%（95%CI，50.8 至 81.5）。在随访期间未检测到 DENV-3 和 DENV-4。接种布坦坦-DV 后 21 天内，与安慰剂相比，更常见与疫苗相关的全身性不良事件（58.3%的参与者，45.6%）。
一剂布坦坦-DV 可预防症状性 DENV-1 和 DENV-2，无论基线时的登革热血清状态如何，通过 2 年的随访。（由布坦坦研究所和其他机构资助；DEN-03-IB 临床试验.gov 编号，NCT02406729，以及世卫组织 ICTRP 编号，U1111-1168-8679。）
