Full article in Open-access

 

Saranya Sridhar, M.B., B.S., D.Phil., Alexander Luedtke, Ph.D., Edith Langevin, M.Sc., Ming Zhu, Ph.D., Matthew Bonaparte, Ph.D., Tifany Machabert, M.Sc., Stephen Savarino, M.D., M.P.H., Betzana Zambrano, M.D., Annick Moureau, M.Sc., Alena Khromava, M.D., M.P.H., Zoe Moodie, Ph.D., Ted Westling, B.S., et al.

PURPOSE:
In efficacy trials of a tetravalent dengue vaccine (CYD-TDV), excess hospitalizations for dengue were observed among vaccine recipients 2 to 5 years of age. Precise risk estimates according to observed dengue serostatus could not be ascertained because of the limited numbers of samples collected at baseline. We developed a dengue anti–nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay and used samples from month 13 to infer serostatus for a post hoc analysis of safety and efficacy.

METHODS:
In a case–cohort study, we reanalyzed data from three efficacy trials. For the principal analyses, we used baseline serostatus determined on the basis of measured (when baseline values were available) or imputed (when baseline values were missing) titers from a 50% plaque-reduction neutralization test (PRNT50), with imputation conducted with the use of covariates that included the month 13 anti-NS1 assay results. The risk of hospitalization for virologically confirmed dengue (VCD), of severe VCD, and of symptomatic VCD according to dengue serostatus was estimated by weighted Cox regression and targeted minimum loss–based estimation.

RESULTS:
Among dengue-seronegative participants 2 to 16 years of age, the cumulative 5-year incidence of hospitalization for VCD was 3.06% among vaccine recipients and 1.87% among controls, with a hazard ratio (vaccine vs. control) through data cutoff of 1.75 (95% confidence interval [CI], 1.14 to 2.70). Among dengue-seronegative participants 9 to 16 years of age, the cumulative incidence of hospitalization for VCD was 1.57% among vaccine recipients and 1.09% among controls, with a hazard ratio of 1.41 (95% CI, 0.74 to 2.68). Similar trends toward a higher risk among seronegative vaccine recipients than among seronegative controls were also found for severe VCD. Among dengue-seropositive participants 2 to 16 years of age and those 9 to 16 years of age, the cumulative incidence of hospitalization for VCD was 0.75% and 0.38%, respectively, among vaccine recipients and 2.47% and 1.88% among controls, with hazard ratios of 0.32 (95% CI, 0.23 to 0.45) and 0.21 (95% CI, 0.14 to 0.31). The risk of severe VCD was also lower among seropositive vaccine recipients than among seropositive controls.

CONCLUSIONS:
CYD-TDV protected against severe VCD and hospitalization for VCD for 5 years in persons who had exposure to dengue before vaccination, and there was evidence of a higher risk of these outcomes in vaccinated persons who had not been exposed to dengue. (Funded by Sanofi Pasteur; ClinicalTrials.gov numbers, NCT00842530, NCT01983553, NCT01373281, and NCT01374516.)

Suscribe to our newsletter

By clicking on the link below, you will be redirected to Youtube. Third-party cookies may then be installed on your browser. These cookies are not implemented directly by the Soladis Clinical Studies site but by the site to which you connect.
Important: these cookies are subject to their own privacy policies and are in no way the responsibility of Soladis.
You can view Youtube's cookie policy by clicking on the following link: Google – Privacy & terms

  Follow Soladis on Youtube

By clicking on the link below, you will be redirected to LinkedIn. Third-party cookies may then be installed on your browser. These cookies are not implemented directly by the Soladis Clinical Studies site but by the social network site to which you connect.
These cookies are subject to their own privacy policies and are in no way the responsibility of Soladis.
You can view LinkedIn's cookie policy by clicking on the following link :  LinkedIn – Cookie Policy

Follow Soladis on LinkedIn

En cliquant sur le lien ci-dessous, vous allez être redirigé vers Youtube. Des cookies tiers peuvent alors être installés sur votre navigateur. Ces cookies ne sont pas implémentés directement par le site Soladis Clinical Studies mais par le site auquel vous vous connectez.
Important : ces cookies sont soumis à leurs propres politiques de confidentialité et ne relèvent en aucun cas de la responsabilité de Soladis.
Vous pouvez consulter la politique de Youtube en matière de cookies en cliquant sur le lien suivant : Google – Règles de confidentialité et conditions d’utilisation

  Suivre Soladis sur Youtube

En cliquant sur le lien ci-dessous, vous allez être redirigé vers LinkedIn. Des cookies tiers peuvent alors être installés sur votre navigateur. Ces cookies ne sont pas implémentés directement par le site Soladis Clinical Studies mais par le site de réseau social auquel vous vous connectez.
Ces cookies sont soumis à leurs propres politiques de confidentialité et ne relèvent en aucun cas de la responsabilité de Soladis.
Vous pouvez consulter la politique de LinkedIn en matière de cookies en cliquant sur le lien suivant : LinkedIn – Politique relative aux cookies

  Suivre Soladis sur LinkedIn