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Vaccine. 2020 Mar 20. pii: S0264-410X(20)30384-4. doi: 10.1016/j.vaccine.2020.03.029. [Epub ahead of print]

Assessment of the long-term efficacy of a dengue vaccine against symptomatic, virologically-confirmed dengue disease by baseline dengue serostatus.

Author information

1
Sanofi Pasteur, Discovery Drive, Swiftwater, PA 18370, USA. Electronic address: Gustavo.Dayan@sanofi.com.
2
Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy l'Etoile, France. Electronic address: Edith.Langevin@sanofi.com.
3
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address: pgilbert@fredhutch.org.
4
Sanofi Pasteur, Discovery Drive, Swiftwater, PA 18370, USA. Electronic address: Yukun.Wu@sanofi.com.
5
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address: zoe@fredhutch.org.
6
Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy l'Etoile, France. Electronic address: Remi.Forrat@sanofi.com.
7
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address: blp7@uw.edu.
8
Sanofi Pasteur, 38 Beach Road #18-11 South Beach Tower, 189767 Singapore, Singapore. Electronic address: Carina.Frago@sanofi.com.
9
Sanofi Pasteur, 38 Beach Road #18-11 South Beach Tower, 189767 Singapore, Singapore.
10
Sanofi Pasteur, Bogotá, Colombia. Electronic address: Margarita.Cortes@sanofi.com.
11
Sanofi Pasteur, Discovery Drive, Swiftwater, PA 18370, USA.
12
Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy l'Etoile, France. Electronic address: Carlos.DiazGranados@sanofi.com.

Abstract

CYD-TDV is a live, attenuated, tetravalent dengue vaccine licensed in 21 countries. We undertook a post-hoc analysis of the long-term efficacy of CYD-TDV during the surveillance expansion phase (SEP) of two Phase III studies (CYD14 in the Asia-Pacific region; CYD15 in Latin America). The SEP included approximately Year 5 and the entire Year 6 of follow-up after the first study injection. Vaccine efficacy against symptomatic virologically-confirmed dengue (VCD) was assessed by participant age (any age, ≥9, <9, 2-5, and 6-8 years at the time of the first injection) and baseline dengue serostatus using a case-cohort framework. Baseline dengue serostatus was estimated by several methods including logistic regression-based multiple imputation (MI) to predict PRNT50 with key predictor being Month 13 (M13) anti-non-structural protein (NS1) titers; superlearner-based imputation by targeted minimum loss based estimation (TMLE); and M13 anti-NS1 titer threshold 9 EU/mL (NS1 M13). There were 436 symptomatic VCD cases (CYD14: n = 360; CYD15: n = 76) during the SEP. Vaccine efficacy in seropositive participants aged ≥9 years was assessed by MI (47.9% [95% CI 19.4; 66.3]), TMLE (53.0% [95% CI 23; 71]), and NS1 M13 (52.4% [95% CI 30.8; 67.3]). Vaccine efficacy estimates were lower in seropositive individuals aged <9 years compared with individuals ≥9 years. Among seropositive individuals aged 2-5 and 6-8 years, vaccine efficacy across the different approaches for assessing serostatus ranged from between -25.7 to 36.9% and 44.4 to 64.7% during the SEP, respectively. In the pooled CYD14/15 data of seronegatives, vaccine efficacy was null to modest. In conclusion, CYD-TDV was shown to maintain efficacy against symptomatic VCD in seropositive participants aged ≥9 years up to six years after the first dose. Persistence of efficacy was also observed in seropositive participants aged 6-8 years.

KEYWORDS:

Asia-Pacific; CYD-TDV; Latin America; Serostatus; Vaccine efficacy

PMID:
32204943
DOI:
10.1016/j.vaccine.2020.03.029
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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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