Overview of expertise of interviewees.

Several tuberculosis (TB) vaccines intended for adults and adolescents are in late-stage clinical trials, but there is limited research into how a new TB vaccine would be introduced. South Africa is at the forefront of TB vaccine research, with involvement in the clinical trials of leading candidates. We sought to understand what the priorities and implementation approach of a potential new TB vaccine in South Africa would be. We conducted semi-structured interviews with 26 stakeholders with different expertise during April and May 2025. Deductive analysis was used to develop a coding framework for thematic content analysis of the data. Stakeholders supported introducing a new TB vaccine in South Africa due to the high disease burden, but feasibility of the roll out was said to depend on vaccine price, cost-effectiveness, efficacy, regulatory approval, and implementation logistics. Efficacy below 50% could raise concerns unless supported by robust modelling demonstrating significant public health impact and cost-effectiveness. Stakeholders preferred a cheaper vaccine course to enable a broad population-based introduction. Priority populations for vaccination included adolescents and adults for a broad population approach, and high-risk groups such as, people living with HIV, healthcare workers and TB household contacts. Whilst a national broad population-based approach was preferred, constraints may result in a phased introduction in high-burden areas and/or targeted vaccination to high-risk groups first. Strong advocacy, detailed cost effectiveness assessments, regulatory alignment, and integrated service delivery were seen as essential to successful implementation. With the introduction of a new TB vaccine potentially as early as 2030, this study provides valuable insights, particularly regarding target populations, that can be utilised for the implementation of a new TB vaccine in South Africa to ensure a successful introduction. Further research is required on vaccine acceptability, TB infection prevalence and modelling to estimate cost effectiveness and budget impact.