Efficacy of a tetravalent dengue vaccine in children in Latin America
Luis Villar, Gustavo Horacio Dayan, José Luis Arredondo-García, Doris Maribel Rivera, Rivaldo Cunha, Carmen Deseda, Humberto Reynales, Maria Selma Costa, Javier Osvaldo Morales-Ramírez, Gabriel Carrasquilla, Luis Carlos Rey, Reynaldo Dietze, Kleber Luz, Enrique Rivas, Maria Consuelo Miranda Montoya, Margarita Cortés Supelano, Betzana Zambrano, Edith Langevin, Mark Boaz, Nadia Tornieporth, Melanie Saville, Fernando Noriega, CYD15 Study Group, Nicolas Jackson, Anna Skipetrova, Florence Sellier-Sandrin, Jean Lang, Vincent Canouet, Linda Urcuyo, José Noguera, Pedro Garbes, Tom Papa, Flávio Henrique Alves de Lima, Amanda Queiroz Soares, Eveline Pipolo Milan, Manoella do Monte Alves, Maria Fabiana da Silva Nascimento, Lilia Maraia Carneiro Camara, Ana Daniela Azoton de Sadovsky, Patricia Marquez Rodrigues, Camila Giuberti, Anamaría Mello M Paniago, Vanessa Gubert Matos, Juliana Quintero, Jaime Carrillo, Víctor Osorio, Héctor Pachón, Reynaldo López, Erwin Pardo, Victor Sierra, Edith Rodríguez, Héctor Velasquez, Libia M Hernández, Elsa Rojas, Jurg Niederbacher, Elham B Mandegari F, Myrna L Vásquez A, Amalia I Sabillón C, Leonor Cristina Benist Damian, Ismael Martin Valencia Camara, María Concepcion Morales Martin, José Maria Remes Troche, Jaime Deseda Tous, Jeffrey Quiñones, José Miguel Fors, Sophie Gallo, Mihaela Tila, Annick Moureau, Mark Talarico, Lizbeth Carmona, Caroline Ruat, Pascale Chermette-Filippi, Nathalie Cochet, Corinne Terle, Leon Ochiai, Joyce Ojeda, Elsa Sarti, Sharon Orlowski, Vivian Gomez, Francisco Garcia, Patricia Eriksson, Diane van der Vliet, Sandra Ibagón, Héctor González, Sandra Mendoza, Flavia Penido, Erica Shinohara, Melina Campos, Marcela Cruz, Ana Claudia Guzmán, Lucia Pérez, Bruno Guy, Béatrice Buffin, Sophia Gailhardou, Maina L'Azou, Laurent Chambonneau, Grenville Marsh, Anne Dagot, Clarisse Plavosin, Jean-Sébastien Persico, Aline Richetin-Guilluy, Margaret Buenzli, Sophie Gilles, Chantal Rotario, Lyn Morgan, Nona Ghanzafari, Alice Padieu-Sequeira, Cauhe Soto, Margaret Manni, Marcelo Turine, Joao Ricardo Filgueiras Tognini, José Quirinho da Silva Filho, Lucila Pereira Dutra Molino, Melissa Fonseca Andrade, Ana Carolina Almeida Oliveira Cheibub, Pryscilla Formiga Figueiredo, Ana Paula David, Cosme Santiado Souza, Ana P Leão Jabur, Alexandra Vilela Gonçalves, Ana C Figueredo Modesto, Paola Poloni Lobo de Aguiar, Adryadne Lyrio Oliveira, Jeovan Figueiredo, Luis Alfredo Nuñez P, Johanna Alejandra Correa Rivera, Lina María Barrera Giraldo, Mónica Patricia Fernánez Monsalve, Luiz Aída Nieto Gutiérrez, Diana Rojas Alvarez, Eduardo Andrés Vásquez Henao, Fabio Dario Otero, Lidia E Canahuati, Delmy E Castillo, Sara A Ordóñez, Marta L Ferrari, Juan R García, Sandra Villagomez M, Jorge F Mendez G, Salvador Gomez, Américo Villareal, Juan Gotos, Edna Zayas, Richard Cortés, Rosaura Aguayo, Margarita Martínez, Franck von Sonnenburg, Celia M Alpuche Aranda, Silvia Regina Marques, José Cordero, Peter Smith, Siripen Kalayanarooj, Quack Seng Hock, Jukka Jokinen, Tran Tin Hien, Raúl Istúriz, Luis Villar, Gustavo Horacio Dayan, José Luis Arredondo-García, Doris Maribel Rivera, Rivaldo Cunha, Carmen Deseda, Humberto Reynales, Maria Selma Costa, Javier Osvaldo Morales-Ramírez, Gabriel Carrasquilla, Luis Carlos Rey, Reynaldo Dietze, Kleber Luz, Enrique Rivas, Maria Consuelo Miranda Montoya, Margarita Cortés Supelano, Betzana Zambrano, Edith Langevin, Mark Boaz, Nadia Tornieporth, Melanie Saville, Fernando Noriega, CYD15 Study Group, Nicolas Jackson, Anna Skipetrova, Florence Sellier-Sandrin, Jean Lang, Vincent Canouet, Linda Urcuyo, José Noguera, Pedro Garbes, Tom Papa, Flávio Henrique Alves de Lima, Amanda Queiroz Soares, Eveline Pipolo Milan, Manoella do Monte Alves, Maria Fabiana da Silva Nascimento, Lilia Maraia Carneiro Camara, Ana Daniela Azoton de Sadovsky, Patricia Marquez Rodrigues, Camila Giuberti, Anamaría Mello M Paniago, Vanessa Gubert Matos, Juliana Quintero, Jaime Carrillo, Víctor Osorio, Héctor Pachón, Reynaldo López, Erwin Pardo, Victor Sierra, Edith Rodríguez, Héctor Velasquez, Libia M Hernández, Elsa Rojas, Jurg Niederbacher, Elham B Mandegari F, Myrna L Vásquez A, Amalia I Sabillón C, Leonor Cristina Benist Damian, Ismael Martin Valencia Camara, María Concepcion Morales Martin, José Maria Remes Troche, Jaime Deseda Tous, Jeffrey Quiñones, José Miguel Fors, Sophie Gallo, Mihaela Tila, Annick Moureau, Mark Talarico, Lizbeth Carmona, Caroline Ruat, Pascale Chermette-Filippi, Nathalie Cochet, Corinne Terle, Leon Ochiai, Joyce Ojeda, Elsa Sarti, Sharon Orlowski, Vivian Gomez, Francisco Garcia, Patricia Eriksson, Diane van der Vliet, Sandra Ibagón, Héctor González, Sandra Mendoza, Flavia Penido, Erica Shinohara, Melina Campos, Marcela Cruz, Ana Claudia Guzmán, Lucia Pérez, Bruno Guy, Béatrice Buffin, Sophia Gailhardou, Maina L'Azou, Laurent Chambonneau, Grenville Marsh, Anne Dagot, Clarisse Plavosin, Jean-Sébastien Persico, Aline Richetin-Guilluy, Margaret Buenzli, Sophie Gilles, Chantal Rotario, Lyn Morgan, Nona Ghanzafari, Alice Padieu-Sequeira, Cauhe Soto, Margaret Manni, Marcelo Turine, Joao Ricardo Filgueiras Tognini, José Quirinho da Silva Filho, Lucila Pereira Dutra Molino, Melissa Fonseca Andrade, Ana Carolina Almeida Oliveira Cheibub, Pryscilla Formiga Figueiredo, Ana Paula David, Cosme Santiado Souza, Ana P Leão Jabur, Alexandra Vilela Gonçalves, Ana C Figueredo Modesto, Paola Poloni Lobo de Aguiar, Adryadne Lyrio Oliveira, Jeovan Figueiredo, Luis Alfredo Nuñez P, Johanna Alejandra Correa Rivera, Lina María Barrera Giraldo, Mónica Patricia Fernánez Monsalve, Luiz Aída Nieto Gutiérrez, Diana Rojas Alvarez, Eduardo Andrés Vásquez Henao, Fabio Dario Otero, Lidia E Canahuati, Delmy E Castillo, Sara A Ordóñez, Marta L Ferrari, Juan R García, Sandra Villagomez M, Jorge F Mendez G, Salvador Gomez, Américo Villareal, Juan Gotos, Edna Zayas, Richard Cortés, Rosaura Aguayo, Margarita Martínez, Franck von Sonnenburg, Celia M Alpuche Aranda, Silvia Regina Marques, José Cordero, Peter Smith, Siripen Kalayanarooj, Quack Seng Hock, Jukka Jokinen, Tran Tin Hien, Raúl Istúriz
Abstract
Background: In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development.
Methods: In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days after the third injection.
Results: A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with 5809 person-years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events.
Conclusions: The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516.).
Source: PubMed