Immune Responses Following a Fractional Intradermal Second Dose of TAK-003 in Dengue-Seropositive Adults: A Randomized Pilot Trial

Background/Objectives: Fractional intradermal administration may offer a dose-sparing approach to dengue vaccination. This randomized pilot study explored the administration of a fractional intradermal second dose of TAK-003 and described immune responses and adverse events in dengue-seropositive adults. Methods: Both groups received a standard 0.5-mL subcutaneous first dose, followed approximately 90 days later by either a standard 0.5-mL subcutaneous second dose or a fractional 0.1-mL intradermal second dose. Twenty-four dengue-seropositive adults were randomized in a 1:1 ratio to the SC–SC or SC–ID group. Anti-dengue IgG and IFN-γ ELISpot responses to DENV peptide pools were assessed at baseline, day 30, and day 120. Immunogenicity analyses were exploratory. Results: All 24 vaccinated participants completed follow-up. Day-30 measurements followed the common subcutaneous first dose and preceded the different second-dose regimens. At day 120, median anti-dengue IgG levels were 141.30 and 146.60 RU/mL in the SC–SC and SC–ID groups, respectively. IFN-γ responses to the tested peptide pools were measurable in both groups. No statistically significant between-group differences were detected at day 120, although the small sample size precludes conclusions of similarity. No serious adverse events were observed. Conclusions: Fractional intradermal administration of the second TAK-003 dose elicited measurable humoral and cellular immune responses and supports the biological feasibility of this dose-sparing approach. Given the exploratory nature and small sample size of this pilot study, these findings warrant confirmation in larger studies.