Immunogenicity of the Cyd-TDV Vaccine in Children and Adolescents: Systematic Review and Meta-Analysis of Randomized Clinical Trials

Dengue is an arboviral disease prevalent in tropical regions. CYD-TDV (Dengvaxia®) is the first licensed vaccine, indicated for seropositive individuals. Clinical studies have demonstrated a variable immune response across the viral serotypes, with higher antibody titers in previously exposed individuals. This study aims to evaluate the immunogenicity of the vaccine based on neutralizing antibody titers induced against the four viral serotypes. We conducted searches in PubMed, Embase and Cochrane databases for randomized clinical trials that evaluated the immunogenicity of the CYD-TDV vaccine, with data on neutralizing antibody titers specific to the four dengue virus serotypes. Statistical analysis was performed using R software (version 4.5.0), with results expressed as geometric means and geometric mean ratios, using a random-effects model and a 5% significance level. Heterogeneity among studies was assessed using the I² statistic. Sensitivity analyses were performed according to data availability. Nine RCTs were included, totaling 24,300 participants, with a mean age of 9.83 years and a baseline seropositivity of 54.99%. The CYD-TDV vaccine demonstrated a significant increase in neutralizing antibody titers against all four dengue virus serotypes. Differences between vaccinated and control groups were: DENV-1 (MD: 132.65; 95% CI: 76.60 to 188.70; p<0.01; I²=95.7%), DENV-2 (MD: 223.75; 95% CI: 125.87 to 321.62; p<0.01; I²=97.2%), DENV-3 (MD: 207.37; 95% CI: 100.08 to 314.67; p<0.01; I² = 95.7%) and DENV-4 (MD: 162.90; 95% CI: 109.41 to 216.40; p<0.01; I²=95.6%). In the combined analysis, MD was 181.03 (95% CI: 140.95 to 221.11; p < 0.01), with high overall heterogeneity (I²=97.2%), indicating a greater immune response in the CYD-TDV group compared with the control group. The results of this meta-analysis confirm that the CYD-TDV vaccine is immunogenic, with a significant increase in neutralizing antibodies against all four dengue virus serotypes. These findings support its use as an effective prevention strategy in endemic areas.