Abstract / Summary
Abstract Recurrent issues with global yellow fever (YF) vaccine supply have highlighted the need for next‑generation YF vaccines that come with simplified and scalable manufacturing processes. Here, we report the first clinical evaluation of Launch-iT YF, a next-generation DNA-based YF vaccine from which live-attenuated YF17D virions are produced upon administration. In this randomized, double-blind, placebo-controlled, dose‑escalation trial (SAFYR), healthy adults (18-40 years) received Launch-iT YF 30 µg (N = 12), 100 µg (N = 24), 300 µg (N = 12), or placebo (N = 16). Launch-iT YF had an acceptable safety profile with limited reactogenicity. A single vaccination induced persistent coordinated humoral and cellular immune responses in participants across Launch‑iT YF groups, with a response rate up to 8/11 (73%) evaluable participants. These findings supported the development of a second-generation Launch-iT YF to improve seroconversion rates, as well as the utilization of this novel technology as a rapidly adaptable vaccine platform. ClinicalTrials.gov identifier: NCT06998004; EU CT number: 2024-511194-29