Efficacy profile of the CYD-TDV dengue vaccine revealed by Bayesian survival analysis of individual-level phase III data.
bayesian statistics
dengue
epidemiology
global health
human
mathematical modelling
survival analysis
vaccine
virus
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
02 07 2021
02 07 2021
Historique:
received:
24
11
2020
accepted:
29
06
2021
pubmed:
6
7
2021
medline:
21
10
2021
entrez:
5
7
2021
Statut:
epublish
Résumé
Sanofi-Pasteur's CYD-TDV is the only licensed dengue vaccine. Two phase three 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. We fit a survival model to individual-level data from both trials, including year 1 of hospital follow-up. We determine efficacy by age, serostatus, serotype and severity, and examine efficacy duration and vaccine action mechanism. 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 against febrile disease. 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. Bill & Melinda Gates Foundation, National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Royal Society. NCT01373281 and NCT01374516.
Sections du résumé
Background
Sanofi-Pasteur's CYD-TDV is the only licensed dengue vaccine. Two phase three 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 1 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 against 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 & Melinda Gates Foundation, National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Royal Society.
Clinical trial number
NCT01373281 and NCT01374516.
Identifiants
pubmed: 34219653
doi: 10.7554/eLife.65131
pii: 65131
pmc: PMC8321579
doi:
pii:
Substances chimiques
Dengue Vaccines
0
Banques de données
ClinicalTrials.gov
['NCT01373281', 'NCT01374516']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R015600/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 213494/Z/18/Z
Pays : United Kingdom
Organisme : Department of Health
ID : PR-OD-1017-20002
Pays : United Kingdom
Informations de copyright
© 2021, Laydon et al.
Déclaration de conflit d'intérêts
DL, ID, WH, GN, NF No competing interests declared, LC Laurent Coudeville is employed by Sanofi-Pasteur
Références
Lancet. 2014 Oct 11;384(9951):1358-65
pubmed: 25018116
Sci Rep. 2019 Jun 28;9(1):9395
pubmed: 31253823
Nat Rev Microbiol. 2010 Dec;8(12 Suppl):S7-16
pubmed: 21079655
N Engl J Med. 2015 Jan 8;372(2):113-23
pubmed: 25365753
Sci Transl Med. 2020 Jan 29;12(528):
pubmed: 31996463
PLoS Med. 2016 Nov 29;13(11):e1002181
pubmed: 27898668
Lancet Infect Dis. 2018 Mar;18(3):245
pubmed: 29276049
Lancet Infect Dis. 2019 May;19(5):465-466
pubmed: 31034385
Science. 2016 Sep 2;353(6303):1033-1036
pubmed: 27701113
Science. 2017 Nov 17;358(6365):929-932
pubmed: 29097492
Lancet Infect Dis. 2016 Jun;16(6):712-723
pubmed: 26874619
N Engl J Med. 2018 Jul 26;379(4):327-340
pubmed: 29897841
Wkly Epidemiol Rec. 2018 Jan 19;93(2):17-30
pubmed: 29350500
Nat Rev Immunol. 2019 Apr;19(4):218-230
pubmed: 30679808
PLoS Comput Biol. 2016 May 23;12(5):e1004951
pubmed: 27213681
Vaccine. 2019 Aug 14;37(35):4848-4849
pubmed: 30424888
Nat Commun. 2018 Sep 7;9(1):3644
pubmed: 30194294
J Infect Dis. 2016 Oct 1;214(7):994-1000
pubmed: 27418050
J Virol Methods. 2018 Jul;257:48-57
pubmed: 29567514
Nature. 2018 May;557(7707):719-723
pubmed: 29795354
Lancet. 2012 Nov 3;380(9853):1559-67
pubmed: 22975340
N Engl J Med. 2015 Sep 24;373(13):1195-206
pubmed: 26214039