Immunogenicity, Safety, and Efficacy of a Tetravalent Dengue Vaccine in Children and Adolescents: An Analysis by Age Group

Abstract

Background: Dengue is an increasing threat to global health. This exploratory analysis evaluated the immunogenicity, safety, and vaccine efficacy (VE) of a live-attenuated tetravalent dengue vaccine (TAK-003) in participants enrolled in the phase 3 DEN-301 trial (NCT02747927), stratified by baseline age (4-5 years, 6-11 years, or 12-16 years).

Methods: Participants were randomized 2:1 to receive 2 doses of TAK-003, administered 3 months apart, or placebo. Dengue serostatus was evaluated at enrolment. VE against virologically confirmed dengue (VCD) and hospitalized VCD; immunogenicity (geometric mean titers [GMTs]); and safety were evaluated per age group through ∼4 years postvaccination.

Results: VE against VCD across serotypes was 43.5% (95% confidence interval [CI]: 25.3%, 57.3%) for 4-5 year-olds; 63.5% (95% CI: 56.9%, 69.1%) for 6-11 year-olds, and 67.7% (95% CI: 57.8%, 75.2%) for 12-16 year-olds. VE against hospitalized VCD was 63.8% (95% CI: 21.1%, 83.4%), 85.1% (95% CI: 77.1%, 90.3%), and 89.7% (95% CI: 77.9%, 95.2%), for the 3 age groups, respectively. GMTs remained elevated against all 4 serotypes for ∼4 years postvaccination, with no evident differences across age groups. No clear differences in safety by age were identified.

Conclusions: This exploratory analysis shows TAK-003 was efficacious in dengue prevention across age groups in children and adolescents 4-16 years of age living in dengue endemic areas. Relatively lower VE in 4-5 year-olds was potentially confounded by causative serotype distribution, small sample size, and VE by serotype, and should be considered in benefit-risk evaluations in this age group.

Keywords: child; dengue vaccine; efficacy; immunogenicity; safety.

Figure 1.

Causative serotype of (A) VCD cases and (B) hospitalized VCD cases in the placebo group by age group (safety set). Abbreviation: VCD, virologically confirmed dengue.

Figure 2.

Efficacy against (A) VCD and (B) hospitalized VCD from the first vaccination to end of Part 3 by age group and baseline serostatus (safety set). Abbreviation: CI, confidence interval; VCD, virologically confirmed dengue.

Figure 3.

GMTs of neutralizing antibodies over time by age group in (A) baseline seronegative and (B) baseline seropositive participants (PPS immunogenicity subset). Note that not all participants may have had evaluable samples at each timepoint. Abbreviations: CI, confidence interval; GMT, geometric mean titer; PPS, per-protocol set.