Background 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, in this study; we sought to understand what the interest, priorities and roll out approach of a potential new TB vaccine in South Africa would be.

Methods We conducted semi-structured interviews with stakeholders with different expertise to understand their approach to the implementation of a new TB vaccine. A total of 26 stakeholders were interviewed during April and May 2025. Deductive analysis was used to develop a coding framework for thematic content analysis of the data.

Results 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 maximise availability and enable a broad population-based introduction. Priority populations for vaccination included adolescents and adults in the case of a broad population approach, and high-risk groups such as, people living with HIV, healthcare workers, TB household contacts, miners, prisoners and people living with diabetes. Whilst a national broad population-based approach was preferred, constraints may result in a phased rollout in high-burden areas and/or targeted vaccination to high-risk groups first. Strong advocacy, detailed cost effectiveness and cost benefit assessments, regulatory alignment, and integrated service delivery were seen as essential to successful implementation.

Conclusions 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 its introduction is successful. Further work is required on vaccine acceptability and TB infection prevalence and modelling to estimate cost effectiveness and budget impact.

KAT, CO, TN MK,VD, DG, OR, RAC, WJ, FA, SC, JS and RGW have no competing interests. GJC is funded by the Gates Foundation through a grant to the Aurum Institute to implement a first-in-human TB vaccine trial. GJC is the Chair of the WHO Technical Advisory Group on Evidence for Clinical and Policy Considerations for New Tuberculosis (TB) Vaccines.

This work was funded by Wellcome Trust (310728/Z/24/Z, 218261/Z/19/Z). KAT is funded by Wellcome Trust (310728/Z/24/Z). RAC was funded by Open Philanthropy/Good Ventures (GV673606227), Wellcome Trust (310728/Z/24/Z), BMGF (INV-001754) and NIH (G-202303-69963, R-202309-71190) to LSHTM. RGW is also funded by the Wellcome Trust (310728/Z/24/Z, 218261/Z/19/Z), NIH (1R01AI147321-01, G-202303-69963, R-202309-71190), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (INV-004737, INV-035506), Open Philanthropy/Good Ventures (GV673606227), and the WHO (2020/985800-0). Co-authors at CHAI (CO, VD, DG & OR) received funding from the Gates Foundation (INV-059503).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

All participants gave informed consent digitally prior to the interviews. The study was approved by the London School of Hygiene & Tropical Medicine Ethics Committee (31511 /RR/37396) and the University of the Witwatersrand Johannesburg Human Research Ethics Committee (250102).

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We cannot share the dataset as we ensured confidentiality to all of our interviewees, and the data could be linked to them. As such, we are unable to provide the anonymised dataset. However, we are happy to share the data upon request to interested, qualified researchers. Please contact Katherine Thomas (Katherine.thomas1lshtm.ac.uk) or Richard White (PI and co-last author) richard.whitelshtm.ac.uk. Data will be stored on a secure server for 2 years, and researcher notes will be stored in a locked cabinet. Data will be managed by the project coordinator and will only be accessible by the study team, under the guidance of the PI. Interested researchers will be asked to complete a data sharing agreement on request for access to the anonymised data. Although the authors cannot make their study’s data publicly available at the time of publication, all authors commit to make the data underlying the findings described in this study fully available without restriction to those who request the data.