Live-attenuated chikungunya vaccine in children: a randomized phase 2 trial.

Currently, no licensed vaccine is available against chikungunya virus (CHIKV) in children aged less than 12 years. In this phase 2, observer-blind, randomized, dose-response trial we evaluated the tolerability (solicited adverse events (AEs)), safety (unsolicited AEs) and immunogenicity of a live-attenuated CHIKV vaccine (VLA1553) in healthy children aged 1-11 years in endemic countries. Here we provide a prespecified interim analysis to 28 days after vaccination. Participants (n = 304) received either a half dose (n = 119) or a full dose (n = 124) of VLA1553, or active control meningococcal vaccine (Nimenrix) (n = 61). The primary endpoint was the incidence and severity of solicited AEs within 14 days after vaccination. Secondary endpoints included unsolicited AEs, medically attended AEs, serious AEs, AEs of special interest and immunogenicity through 28 days after vaccination. For the primary endpoint, there were no statistically significant differences between the VLA1553 groups and control for each age group nor between age groups (1-2, 3-6 and 7-11 years). Overall, the most frequently reported solicited injection site AEs were tenderness (10.9%) and pain (8.6% of participants); the most frequently reported solicited systemic AEs were fever (12.5%) and headache (11.5%; participants aged 7-11 years and 3-6 years only, (headache was not solicited in participants aged 1-2 years)). For the secondary safety endpoints, the most common unsolicited AEs were infections and infestations (10.0-20.5%) and the most common medically attended AE overall was fever (2.6%), with no differences for unsolicited AEs or medically attended AEs regardless of vaccine and age group (serious AEs and AEs of special interest were too infrequent for meaningful comparisons). Anti-CHIKV neutralizing antibody titers were higher in the full-dose than the half-dose group at days 14 and 28 after vaccination. The trial met its prespecified endpoints and supported the selection of full-dose VLA1553 in future clinical trials in this population, addressing a critical unmet medical need. ClinicalTrials.gov registration: NCT06106581 .