Diana Coronel1, Enid J García-Rivera2, Doris Maribel Rivera3, José Luis Arredondo-García4, Reynaldo Dietze5, Ana Paula Perroud6, Margarita Cortés7, Matthew Bonaparte8, Hao Wang9, Anke Pagnon10, Frédérique Jantet-Blaudez10, Luis Andrey Rojas Peñalosa11, Gustavo Dayan12, Betzana Zambrano13, Carlos A DiazGranados14, Fernando Noriega15. 1. From the Clinical Sciences, Sanofi Pasteur, Mexico City, Mexico. 2. Endowed Health Services Research Center, University of Puerto Rico School of Medicine, Medical Sciences Campus, San Juan, 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. Global Health, Sanofi Pasteur, Bogotá, Colombia. 8. Global Clinical Immunology, Sanofi Pasteur, Swiftwater, Pennsylvania. 9. Clinical Sciences and Operations, Sanofi, Beijing, China. 10. Research and External Innovation Department, Sanofi Pasteur, Marcy l'Etoile, France. 11. Departamento de Producción, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción, Paraguay. 12. Clinical Sciences, Sanofi Pasteur, Swiftwater, Pennsylvania. 13. Clinical Sciences, Sanofi Pasteur, Montevideo, Uruguay. 14. Global Clinical Science, Sanofi Pasteur, Marcy l'Etoile, France. 15. Global Clinical Sciences, Sanofi Pasteur, Swiftwater, Pennsylvania.
Abstract
BACKGROUND: We previously described an increased immune response 28 days after a booster dose of the live, attenuated, tetravalent dengue vaccine (CYD-TDV) in healthy adolescents and adults in Latin America (CYD64, NCT02623725). This follow-up study evaluated immune response persistence and safety of a CYD-TDV booster dose up to Month (M) 24 post-booster. METHODS: This study included 250 participants who previously received 3 primary doses of CYD-TDV in the CYD13 (NCT00993447) and CYD30 (NCT01187433) studies, and who were randomized 4-5 years later to receive aCYD-TDV booster or placebo (3:1). Dengue neutralizing antibodies against the parental dengue virus strains were assessed using the plaque reduction neutralization test (PRNT50) at M6, M12, and M24 post-booster. Post-booster memory B-cell responses were assessed in a subset of participants using the FluoroSpot assay up to M12 post-booster. RESULTS: In the CYD-TDV group (n = 187), dengue neutralizing antibody geometric mean titers (GMTs) declined from the peak at day 28 through to M24 for all serotypes. GMTs at M24 were similar to those at pre-booster among baseline dengue seropositives. A similar trend was observed for baseline dengue seronegatives, albeit at a lower magnitude. Previous vaccination-induced detectable B-cell memory responses in seropositives and seronegatives that decreased to pre-booster levels at M12 post-booster. The CYD-TDV booster dose was well-tolerated. CONCLUSIONS: In baseline dengue seropositives, following a CYD-TDV booster dose administered 4-5 years after primary immunization, dengue neutralizing antibody GMTs and B-cell memory responses peaked in the short-term before gradually decreasing over time. A CYD-TDV booster dose could improve protection against dengue during outbreak periods.
RCT Entities:
BACKGROUND: We previously described an increased immune response 28 days after a booster dose of the live, attenuated, tetravalent dengue vaccine (CYD-TDV) in healthy adolescents and adults in Latin America (CYD64, NCT02623725). This follow-up study evaluated immune response persistence and safety of a CYD-TDV booster dose up to Month (M) 24 post-booster. METHODS: This study included 250 participants who previously received 3 primary doses of CYD-TDV in the CYD13 (NCT00993447) and CYD30 (NCT01187433) studies, and who were randomized 4-5 years later to receive a CYD-TDV booster or placebo (3:1). Dengue neutralizing antibodies against the parental dengue virus strains were assessed using the plaque reduction neutralization test (PRNT50) at M6, M12, and M24 post-booster. Post-booster memory B-cell responses were assessed in a subset of participants using the FluoroSpot assay up to M12 post-booster. RESULTS: In the CYD-TDV group (n = 187), dengue neutralizing antibody geometric mean titers (GMTs) declined from the peak at day 28 through to M24 for all serotypes. GMTs at M24 were similar to those at pre-booster among baseline dengue seropositives. A similar trend was observed for baseline dengue seronegatives, albeit at a lower magnitude. Previous vaccination-induced detectable B-cell memory responses in seropositives and seronegatives that decreased to pre-booster levels at M12 post-booster. The CYD-TDV booster dose was well-tolerated. CONCLUSIONS: In baseline dengue seropositives, following a CYD-TDV booster dose administered 4-5 years after primary immunization, dengue neutralizing antibody GMTs and B-cell memory responses peaked in the short-term before gradually decreasing over time. A CYD-TDV booster dose could improve protection against dengue during outbreak periods.
Authors: Cillian Gartlan; Tom Tipton; Francisco J Salguero; Quentin Sattentau; Andrew Gorringe; Miles W Carroll Journal: Front Immunol Date: 2022-04-04 Impact factor: 8.786