Analysis of Hospitalized and Severe Dengue Cases Over the 6 years of Follow-up of the Tetravalent Dengue Vaccine (CYD-TDV) Efficacy Trials in Asia and Latin America.


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
15 09 2021
Historique:
received: 01 06 2020
pubmed: 7 4 2021
medline: 8 10 2021
entrez: 6 4 2021
Statut: ppublish

Résumé

CYD-TDV, a live, attenuated, tetravalent dengue vaccine, has been approved for the prevention of symptomatic dengue in previously dengue exposed individuals. This post hoc analysis assessed hospitalized and severe virologically confirmed dengue (VCD) over the complete 6-year follow-up of 3 CYD-TDV efficacy studies (CYD14, CYD15, and CYD23/CYD57). The main outcomes were hazard ratios (HRs) for hospitalized or severe VCD by baseline dengue serostatus, focusing on those who were seropositive, and by age at immunization (<9 years/≥9 years). Baseline dengue serostatus was measured or inferred using several methods. Hospitalized VCD cases were characterized in terms of clinical signs and symptoms and wild-type viremia level. Antibody persistence was assessed up to 5 years after the last injection. In those aged ≥9 years and baseline seropositive, CYD-TDV protected against hospitalized and severe VCD over 6 years compared to placebo (HR [95% confidence interval] multiple imputation from month 0 method, .19 [.12-.30] and .15 [.06-.39]; other methods were consistent). Vaccine protection was observed over the different study periods, being highest during the first 2 years. Evidence for a decreased risk of hospitalized and severe VCD was also observed in seropositive participants aged 6-8 years. Clinical signs and symptoms, and quantified dengue viremia from participants with hospitalized VCD were comparable between groups. CYD-TDV demonstrated robust protection against hospitalized and severe VCD over the entire 6-year follow-up in participants who were seropositive and ≥9 years old. Protection was also observed in seropositive 6-8 year-olds. Clinical Trials Registration: NCT00842530, NCT01983553, NCT01373281, NCT01374516.

Sections du résumé

BACKGROUND
CYD-TDV, a live, attenuated, tetravalent dengue vaccine, has been approved for the prevention of symptomatic dengue in previously dengue exposed individuals. This post hoc analysis assessed hospitalized and severe virologically confirmed dengue (VCD) over the complete 6-year follow-up of 3 CYD-TDV efficacy studies (CYD14, CYD15, and CYD23/CYD57).
METHODS
The main outcomes were hazard ratios (HRs) for hospitalized or severe VCD by baseline dengue serostatus, focusing on those who were seropositive, and by age at immunization (<9 years/≥9 years). Baseline dengue serostatus was measured or inferred using several methods. Hospitalized VCD cases were characterized in terms of clinical signs and symptoms and wild-type viremia level. Antibody persistence was assessed up to 5 years after the last injection.
RESULTS
In those aged ≥9 years and baseline seropositive, CYD-TDV protected against hospitalized and severe VCD over 6 years compared to placebo (HR [95% confidence interval] multiple imputation from month 0 method, .19 [.12-.30] and .15 [.06-.39]; other methods were consistent). Vaccine protection was observed over the different study periods, being highest during the first 2 years. Evidence for a decreased risk of hospitalized and severe VCD was also observed in seropositive participants aged 6-8 years. Clinical signs and symptoms, and quantified dengue viremia from participants with hospitalized VCD were comparable between groups.
CONCLUSIONS
CYD-TDV demonstrated robust protection against hospitalized and severe VCD over the entire 6-year follow-up in participants who were seropositive and ≥9 years old. Protection was also observed in seropositive 6-8 year-olds. Clinical Trials Registration: NCT00842530, NCT01983553, NCT01373281, NCT01374516.

Identifiants

pubmed: 33822015
pii: 6210060
doi: 10.1093/cid/ciab288
pmc: PMC8442794
doi:

Substances chimiques

Antibodies, Viral 0
Dengue Vaccines 0
Vaccines, Attenuated 0
Vaccines, Combined 0

Banques de données

ClinicalTrials.gov
['NCT00842530', 'NCT01983553', 'NCT01374516', 'NCT01373281']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1003-1012

Subventions

Organisme : Sanofi Pasteur

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

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Auteurs

Rémi Forrat (R)

Clinical Sciences, Sanofi Pasteur, Marcy l'Etoile, France.

Gustavo H Dayan (GH)

Clinical Sciences Sanofi Pasteur, Swiftwater, Pennsylvania, USA.

Carlos A DiazGranados (CA)

Clinical Sciences Sanofi Pasteur, Swiftwater, Pennsylvania, USA.

Matthew Bonaparte (M)

Translation Sciences and Biomarkers, Sanofi Pasteur, Swiftwater, Pennsylvania, USA.

Thelma Laot (T)

Global Clinical Science, Sanofi Pasteur, Taguig City, Philippines.

Maria Rosario Capeding (MR)

Research Institute for Tropical Medicine, Medical Department, Muntinlupa, Philippines.

Leilani Sanchez (L)

Global Clinical Science, Sanofi Pasteur, Taguig City, Philippines.

Diana Leticia Coronel (DL)

Clinical Sciences, Sanofi Pasteur, Mexico City, Mexico.

Humberto Reynales (H)

Centro de Atencion e Investigación Médica, Caimed S.A.S, Bogotá, Colombia.

Danaya Chansinghakul (D)

Research & Development, Sanofi Pasteur, Bangkok, Thailand.

Sri Rezeki S Hadinegoro (SRS)

Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta, Indonesia.

Ana Paula Perroud (AP)

Clinical Sciences, Sanofi Pasteur, São Paulo, Brazil.

Carina Frago (C)

Clinical Sciences, Sanofi Pasteur, Singapore.

Betzana Zambrano (B)

Clinical Sciences, Sanofi Pasteur, Uruguay.

Tifany Machabert (T)

Clinical Sciences, Sanofi Pasteur, Marcy l'Etoile, France.

Yukun Wu (Y)

Clinical Sciences Sanofi Pasteur, Swiftwater, Pennsylvania, USA.

Alexander Luedtke (A)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Brenda Price (B)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Claire Vigne (C)

Clinical Sciences, Sanofi Pasteur, Marcy l'Etoile, France.

Owen Haney (O)

Global Pharmacovigilance, Sanofi Pasteur, Swiftwater, Pennsylvania, USA.

Stephen J Savarino (SJ)

Translation Sciences and Biomarkers, Sanofi Pasteur, Swiftwater, Pennsylvania, USA.

Alain Bouckenooghe (A)

Clinical Sciences, Sanofi Pasteur, São Paulo, Brazil.

Fernando Noriega (F)

Clinical Sciences Sanofi Pasteur, Swiftwater, Pennsylvania, USA.

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Classifications MeSH