Efficacy after 1 and 2 doses of CYD-TDV in dengue endemic areas by dengue serostatus. Issue 41 (22nd September 2020)

• Record Type: Journal Article
• Authors: Dayan, Gustavo H.; Langevin, Edith; Forrat, Remi; Zambrano, Betzana; Noriega, Fernando; Frago, Carina; Bouckenooghe, Alain; Machabert, Tifany; Savarino, Stephen; DiazGranados, Carlos A.
• Is Part Of: Vaccine. Volume 38:Issue 41(2020)
• Page Start: 6472
• Page End: 6477
• Publication Date: 2020-09-22
• Subjects: CYD-TDV -- Vaccine efficacy -- Serostatus -- Inter-dose -- Asia-Pacific -- Latin America; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2020.07.056
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: CYD-TDV was efficacious in dengue seropositives aged ≥ 9 years from dose 1 to M25. Inter-dose efficacy was similar to that post-dose 3 in seropositives aged ≥ 9 years. Immunogenicity data are in line with CYD-TDV efficacy results in dengue seropositives. CYD-TDV inter-dose efficacy was null to modest in dengue seronegatives of any age. Abstract: A simplified dose regimen of the live, attenuated, tetravalent dengue vaccine (CYD-TDV) could have the potential to facilitate easier implementation of immunization programs against symptomatic virologically-confirmed dengue (VCD) in dengue seropositive individuals aged ≥ 9 years. This post-hoc analysis of two Phase III studies (CYD14 [NCT01373281] and CYD15 [NCT01374516]) in dengue endemic areas assessed the efficacy of CYD-TDV by dengue serostatus between dose 1 and 2 (at Month [M] 6), between dose 2 and 3 (at M12), and from dose 3 to M25. Baseline dengue serostatus (seropositive or seronegative) was determined based on measured dengue neutralizing antibody titers with the 50% plaque reduction neutralization test (PRNT50 ) or ascertained by logistic regression-based multiple imputation (MI) to predict PRNT50 . Vaccine efficacy against symptomatic VCD was assessed by age and baseline dengue serostatus using a case-cohort framework. Dengue neutralizing antibody geometric mean titers (GMTs) were measured with the PRNT50 at 28 days post-dose 2 and 3. Vaccine efficacy estimates in seropositive participants aged ≥ 9 years at post-dose 1, 2, and 3 were 80.5% (95% CI, 66.2, 88.7), 82.0% (95% CI, 70.5, 89.0), and 75.2% (95% CI, 65.9, 81.9), respectively. In seropositive participants aged < 9 years, vaccine efficacy estimates were 48.5% (95% CI, –24.3, 78.6), 68.3% (95% CI, 34.5, 84.7), and 65.3% (95% CI, 40.2, 79.9), respectively. CYD-TDV efficacy was null to modest after any dose in seronegative participants, regardless of age group. Seropositive participants aged ≥ 9 years in the CYD-TDV group had GMTs post-dose 3 that did not exceed those observed post-dose 2. In conclusion, CYD-TDV has high efficacy against VCD from the first dose through to M25, with estimates at post-dose 1 and 2 similar to or higher than those at post-dose 3 in seropositive participants aged ≥ 9 years, consistent with immunogenicity data.