Diana Coronel1, Enid J García-Rivera2, Maribel Rivera3, José Luis Arredondo-García4, Reynaldo Dietze5, Ana Paula Perroud6, Margarita Cortés7, Matthew Bonaparte8, Jessie Zhao9, Mihaela Tila10, Nick Jackson10, Betzana Zambrano11, Fernando Noriega8. 1. From the Clinical Sciences Sanofi Pasteur, Mexico City, Mexico. 2. School of Medicine, Hospital UPR Carolina, University of Puerto Rico, Puerto Rico. 3. Inversiones en Investigación Médica S.A. INVERIME S.A, Tegucigalpa, Honduras. 4. Instituto Nacional de Pediatría Clinical Research Unit, Mexico City, Mexico. 5. Universidade Federal do Espirito Santo, Núcleo de Doenças Infecciosas/CBM/UFES, Vitoria, Brazil. 6. Clinical Sciences Sanofi Pasteur, Sao Paulo, Brazil. 7. Clinical Sciences Sanofi Pasteur, Bogota, Colombia. 8. Clinical Sciences Sanofi Pasteur, Swiftwater, PA. 9. Clinical Sciences Sanofi Pasteur, Beijing, China. 10. Sanofi, Paris, France. 11. Clinical Sciences Sanofi Pasteur, Montevideo, Uruguay.
Abstract
BACKGROUND: The tetravalent dengue vaccine (CYD-TDV, Dengvaxia, Sanofi Pasteur) demonstrated efficacy in 2 previous phase III trials conducted in endemic countries. Neutralizing antibodies (NAbs) elicited by 3 doses of this vaccine have been associated with efficacy. Long-term follow-up data has shown that NAb immune responses tend to wane over time, after the third dose. This study compared the immune response elicited by a booster (4th) dose of CYD-TDV with the immune responses from the same participants obtained post-dose 3 of the primary series administered 4-5 years earlier. METHODS: This multicenter, observer-blind, randomized, placebo-controlled, phase II noninferiority trial was conducted in healthy adolescents and adults in dengue endemic countries of Latin America (Colombia, Honduras, Brazil, Mexico and Puerto Rico). All participants had been immunized with 3 doses of CYD-TDV in phase II studies conducted 4-5 years earlier. NAb levels against each dengue virus serotype 28 days postbooster or placebo injection were reported. RESULTS: A total of 187 participants receivedCYD-TDV and 64 received placebo. Prospectively defined noninferiority criteria for dengue NAbs after the booster dose compared with postdose 3 were met for all 4 serotypes. Prospectively defined superiority criteria were met for 3 of the 4 serotypes. CONCLUSIONS: Antidengue NAb levels can be boosted to levels at least as high as, or higher than those observed after completion of the primary 3-dose series, with an additional dose of CYD-TDV 4-5 years after the standard 3-dose vaccination schedule.
RCT Entities:
BACKGROUND: The tetravalent dengue vaccine (CYD-TDV, Dengvaxia, Sanofi Pasteur) demonstrated efficacy in 2 previous phase III trials conducted in endemic countries. Neutralizing antibodies (NAbs) elicited by 3 doses of this vaccine have been associated with efficacy. Long-term follow-up data has shown that NAb immune responses tend to wane over time, after the third dose. This study compared the immune response elicited by a booster (4th) dose of CYD-TDV with the immune responses from the same participants obtained post-dose 3 of the primary series administered 4-5 years earlier. METHODS: This multicenter, observer-blind, randomized, placebo-controlled, phase II noninferiority trial was conducted in healthy adolescents and adults in dengue endemic countries of Latin America (Colombia, Honduras, Brazil, Mexico and Puerto Rico). All participants had been immunized with 3 doses of CYD-TDV in phase II studies conducted 4-5 years earlier. NAb levels against each dengue virus serotype 28 days postbooster or placebo injection were reported. RESULTS: A total of 187 participants received CYD-TDV and 64 received placebo. Prospectively defined noninferiority criteria for dengue NAbs after the booster dose compared with postdose 3 were met for all 4 serotypes. Prospectively defined superiority criteria were met for 3 of the 4 serotypes. CONCLUSIONS: Antidengue NAb levels can be boosted to levels at least as high as, or higher than those observed after completion of the primary 3-dose series, with an additional dose of CYD-TDV 4-5 years after the standard 3-dose vaccination schedule.