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Clinical Trial
. 2021 Sep 1;40(9):856-863.
doi: 10.1097/INF.0000000000003220.

Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Tdap Vaccine: Randomized Phase IIIb Trial in Healthy Participants 9-60 Years of Age in the Philippines

Jaime Santos  1 , May Emmeline Montellano  2 , Rontgene Solante  3 , Nicole Perreras  4 , Stéphanie Meyer  5 , Myew-Ling Toh  5 , Céline Zocchetti  5 , Claire Vigne  5 , Cesar Mascareñas  6
Affiliations
Clinical Trial

Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Tdap Vaccine: Randomized Phase IIIb Trial in Healthy Participants 9-60 Years of Age in the Philippines

Jaime Santos et al. Pediatr Infect Dis J. .

Abstract

Background: Incorporating dengue vaccination into existing childhood vaccination programs could increase vaccine coverage. This study assessed the safety and immunogenicity of concomitant versus sequential administration of the combined tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine and the tetravalent dengue vaccine (CYD-TDV).

Methods: This phase IIIb, randomized, open-label, multicenter study was conducted in the Philippines in individuals 9-≤60 years of age (NCT02992418). Participants were to receive 3 CYD-TDV doses 6 months apart, the first dose administered either concomitantly or sequentially (28 days post-Tdap). Antibody levels were measured at baseline and 28 days post-first doses of Tdap vaccine and CYD-TDV, using enzyme-linked immunosorbent assay (pertussis, tetanus), micrometabolic inhibition test-toxin neutralization assay (diphtheria) and plaque reduction neutralization test (dengue). Immunogenicity was assessed for all participants, and statistical analysis reported for baseline dengue seropositive participants. Safety was assessed throughout.

Results: Among 688 randomized participants, 629 (91.4%) were baseline dengue seropositive (concomitant group, n = 314 and sequential group, n = 315). After the first dose, non-inferiority of immune responses between concomitant and sequential vaccination was achieved; between-group geometric mean antibody concentration ratios were close to 1 for anti-PT, anti-FHA, anti-PRN and anti-FIM, between-group differences in percent achieving seroprotection (titers ≥0.1 IU/mL) were 0.26% (diphtheria) and 0.66% (tetanus), and between-group geometric mean antibody titer ratios were close to 1 for dengue serotypes 1-4. Safety profiles in both study groups were comparable.

Conclusions: CYD-TDV and Tdap vaccine administered concomitantly or sequentially in baseline dengue seropositive participants elicited comparable immunogenicity and safety profiles.

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Conflict of interest statement

T.C.M., C.V., C.Z., M.-L.T. and S.M. are employees of Sanofi Pasteur and may hold shares and/or stock options in the company. The other authors have no conflicts of interest to disclose.

Figures

FIGURE 1.
FIGURE 1.
GMCs of antibodies against pertussis antigens (PT, FHA, PRN and FIM; A–D) and seroprotection* rates (E and F) of antibodies against diphtheria and tetanus toxoids at baseline (pre-Tdap dose) and 28 days post-Tdap dose given concomitantly or sequentially with CYD-TDV in baseline dengue seropositive participants—FAS. *Seroprotection of antibodies against DT or TT was defined as antibody concentrations ≥0.1 IU/mL. FSA indicates full analysis set.
FIGURE 2.
FIGURE 2.
Dengue geometric mean neutralizing antibody titers for each serotype at baseline (pre-dose 1) and 28 days post-dose 1 of CYD-TDV administered concomitantly or sequentially with Tdap vaccine in baseline dengue seropositive participants—FAS. FSA indicates full analysis set.
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