With more than 1.4 million deaths a year, TB is a major global public health challenge, especially in low- and middle-income countries. However, despite the huge global burden of disease, no new vaccine has been introduced since Bacille Calmette-Guérin (BCG) in the 1920s.
It is widely recognized that safe and effective vaccines are a critical component for reaching the global TB targets that have been specified in the World Health Organization’s End TB Strategy, the Sustainable Development Goals, and at the United Nations High-Level Meeting on TB in 2018.
The roadmap was developed through a highly collaborative process
The EDCTP and AIGHD’s TB vaccine roadmap has been developed through an iterative global consultative process and in close collaboration with the WHO.
Earlier this year, the AIGHD invited researchers and stakeholders to respond to a public consultation and express their views on aspects of the draft roadmap before it was finalized.
The consultation led to the identification of three priorities areas (now incorporated in the final roadmap):
1. Diversify the pipeline
Early-stage R&D has focused on a limited number of Mycobacterium tuberculosis (Mtb) antigens and on a very specific type of immune response. There is a need to increase the diversity of the TB vaccine pipeline by focusing on a wider range of antigens, immune responses, and delivery mechanisms.
2. Accelerate clinical development
Clinical evaluation of TB vaccines is slow, high risk, and costly. For one, efficacy in animal models is not a good predictor of efficacy in people, which makes it difficult to prioritise candidates for clinical evaluation. A further important barrier is the lack of well-defined correlates of protection or proxy measures of efficacy. To address these and other clinical development barriers, the roadmap acknowledges a need to:
- Optimise animal models by “back translating” findings from successful clinical trials.
- Optimise alternative endpoints, by establishing the relationship between prevention of disease and other possible endpoints (particularly prevention of infection and prevention of recurrence).
- Harmonise and standardise trial protocols and explore innovative trial designs to improve efficiency.
- Build clinical trial capacity in high-burden countries.
3. Ensure public health impact
Although licensing is seen as a key milestone in new product development, it is only one step in the pathway to public health impact. An end-to-end perspective needs to be adopted so that clinical development is informed by a sound understanding of national decision-making and implementation constraints, and licensing is swiftly followed by efficient programmatic implementation.
3 cross-cutting enabling factors for successful implementation
In addition to the three priority areas, the roadmap acknowledges three cross-cutting enabling factors:
- Funding: The fight against TB remains severely underfunded, and vaccine research is particularly poorly resourced. Efforts are needed to increase funders’ interest in TB vaccine R&D and to attract additional funders.
- Open science: A failure to publish data, particularly negative results, can lead to unnecessary duplication of efforts and research being carried out on approaches unlikely to be successful. Global efforts are required to encourage greater sharing of data.
- Stakeholder engagement: Progress will only be accelerated if all stakeholders collectively and collaboratively focus on the priorities identified in this roadmap.
One hundred years after BCG, the new TB vaccine roadmap brings hope that high TB burden countries can finally gain the benefits of TB prevention and cure through the use of vaccination.