Indonesia presents a complex TB landscape with diverse strains and regional variations, making the Bacillus Calmette-Guérin (BCG) vaccine’s variable efficacy less effective in high-burden areas. This phase I study aims to assess the safety and immunogenicity of a candidate TB vaccine, Ad5-105K, in Indonesian adults aged 18-49 years, a demographic critical to TB transmission dynamics. The primary objective is to rigorously evaluate the vaccine’s safety profile, with close monitoring of adverse events. Secondary objectives include assessing immunogenicity and exploring a dose-finding strategy to identify the most effective and safe dosage. The study adopts a randomized, open-label, placebo-controlled, and dose-finding design, enhancing the reliability of safety and immunogenicity assessments. The successful execution of this trial is crucial for subsequent vaccine development phases, providing essential data to tailor the vaccine for effective TB prevention in Indonesia, with the potential to significantly reduce the TB burden and support the nation’s journey towards effective TB prevention.