Live, Attenuated, Tetravalent Butantan–Dengue Vaccine in Children and Adults
Authors: Esper G Kallás, Monica A T Cintra, José A Moreira, Elizabeth G Patiño, Patricia Emilia Braga, Juliana C V Tenório, Vanessa Infante, Ricardo Palacios, Marcus Vínicius Guimarães de Lacerda, Dhelio Batista Pereira, Allex Jardim da Fonseca, Ricardo Queiroz Gurgel, Ivo Castelo-Branco Coelho, Cor Jesus Fernandes Fontes, Ernesto T A Marques, Gustavo Adolfo Sierra Romero, Mauro Martins Teixeira, André M Siqueira, Aldina Maria Prado Barral, Viviane Sampaio Boaventura, Fabiano Ramos, Erivaldo Elias Júnior, José Cassio de Moraes, Dimas T Covas, Jorge Kalil, Alexander Roberto Precioso, Stephen S Whitehead, Alejandra Esteves-Jaramillo, Tulin Shekar, Jung-Jin Lee, Julieta Macey, Sabrina Gozlan Kelner, Beth-Ann G Coller, Fernanda Castro Boulos, Mauricio L Nogueira
Journal: New England Journal of Medicine (2024)

BackgroundButantan–Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed.MethodsIn 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.Download a PDF of the Research Summary.ResultsOver 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%).ConclusionsA 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.) Quick Take Butantan–Dengue Vaccine in Children and Adults 2m 9s