Adult Immunogenicity and Descriptive Safety of TAK-003 Dengue Vaccination: A Systematic Review and Meta-analysis

Background: Adult TAK-003 data differ by formulation, baseline dengue status, coadministration, and outcome definition. Objective: To synthesize adult immunogenicity and safety of the licensed two-dose final formulation of TAK-003. Methods: We searched PubMed, Scopus, CENTRAL-derived records, registries, regulatory sources, and citations to the final search update. Screening, extraction, appraisal, and analysis used a reproducible computational workflow without independent duplicate verification. Seropositivity and 270-day serious adverse event (SAE) risk were modeled with binomial-normal logit models; comparative reactogenicity used random-effects risk ratios with modified Hartung-Knapp intervals. Certainty was graded by outcome, and a sensitivity analysis added the single-arm DEN307 cohort. Results: Of 1,090 records, 606 unique records (553 publications and 53 registry records) were screened; 473 publications were excluded and 80 were retrieved. Five trials supplied quantitative outcomes. Among 620 baseline-seronegative adults, pooled seropositivity about 30 days after dose 2 was 98.7% for DENV-1 (95% CI 95.8–99.6), 99.0% for DENV-2 (97.9–99.6), 96.9% for DENV-3 (95.2–98.0), and 98.4% for DENV-4 (97.0–99.1). With DEN307 added, estimates were 98.8%, 99.2%, 97.1%, and 98.5% (752 participants per serotype). Across four cohorts, 29/1,468 participants had an SAE through day 270 (pooled risk 2.0%, 95% CI 1.4–2.8). Pain and headache estimates, each from two studies, were highly imprecise. Conclusion: Final-formulation TAK-003 gave high short-term seropositivity in selected adult trial populations. The SAE risk was uncontrolled and does not establish comparative safety. Certainty was low or very low, and inference is limited by study size, surrogate outcomes, and uncontrolled safety data.