Efficacy profile of the CYD-TDV dengue vaccine revealed by Bayesian survival analysis of individual-level Phase III data
- Imperial College London, United Kingdom
- Sanofi-Pasteur, France
Abstract
Background: Sanofi-Pasteur’s CYD-TDV is the only licensed dengue vaccine. Two phase III trials showed higher efficacy in seropositive than seronegative recipients. Hospital follow-up revealed increased hospitalisation in 2-5-year-old vaccinees, where serostatus and age effects were unresolved.
Methods: We fit a survival model to individual-level data from both trials, including year one of hospital follow-up. We determine efficacy by age, serostatus, serotype and severity, and examine efficacy duration and vaccine action mechanism.
Results: Our modelling indicates that vaccine-induced immunity is long-lived in seropositive recipients, and therefore that vaccinating seropositives gives higher protection than two natural infections. Long-term increased hospitalisation risk outweighs short-lived immunity in seronegatives. Independently of serostatus, transient immunity increases with age, and is highest against serotype 4. Benefit is higher in seropositives, and risk enhancement is greater in seronegatives, against hospitalised disease than febrile disease.
Conclusions: Our results support vaccinating seropositives only. Rapid diagnostic tests would enable viable “screen-then-vaccinate” programs. Since CYD-TDV acts as a silent infection, long-term safety of other vaccine candidates must be closely monitored.
Funding: Bill and Melinda Gates Foundation, National Institute for Health Research, UK Medical Research Council, Wellcome Trust.
Data availability
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com. Additional details of the trial designs and data can be found in Sridhar et al (NEJM 2018).All model code is available at https://github.com/dlaydon/DengVaxSurvival, which is linked to in the manuscript. This repository also contains simulated data, generated to closely match the trial data, giving comparable case numbers across strata. When our model is fitted to the simulated data, the resulting parameter estimates closely approximate the results presented in this analysis.
Article and author information
Author details
Funding
Bill and Melinda Gates Foundation
- Daniel J Laydon
- Gemma L Nedjati-Gilani
- Neil M Ferguson
National Institute for Health Research (NIHR: PR-OD-1017-20002)
- Daniel J Laydon
- Gemma L Nedjati-Gilani
- Neil M Ferguson
Medical Research Council (MR/R015600/1)
- Daniel J Laydon
- Ilaria Dorigatti
- Wes R Hinsley
- Gemma L Nedjati-Gilani
- Neil M Ferguson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Laydon et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Efficacy profile of the CYD-TDV dengue vaccine revealed by Bayesian survival analysis of individual-level Phase III data
eLife 10:e65131.
https://doi.org/10.7554/eLife.65131
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