New TB Vaccine Research
Tuberculosis (TB) is the world’s leading cause of death from a single infectious agent next to coronavirus (COVID-19), and one of the leading causes of death from antimicrobial resistance. It is estimated that about one fourth of the world’s population are infected with Mycobacterium tuberculosis (Mtb), of whom 5-10% will develop TB disease during their lifetime. Despite significant advances in reducing mortality in recent decades through improved diagnosis and treatment, TB still causes enormous human suffering, a major economic burden and is one of the major drivers of global inequity. Neonatal BCG vaccination offers partial protection for infants and young children against severe forms of TB, but it does not protect adolescents and adults, who account for the majority of TB transmission. Reaching the WHO End TB Strategy targets of a 95% reduction in TB mortality and a 90% reduction in TB incidence, worldwide, by 2035, will require a new vaccine that is effective across all age groups, particularly adults and adolescents. Vaccines also offer the best chance to contain the accelerating spread of multi-drug resistant tuberculosis. In 2023, WHO’s Director-General launched a TB vaccine accelerator council to facilitate the development of, and equitable access to new TB vaccines.
WHO Preferred product characteristics for new TB vaccines
The development of new TB vaccines is a priority for WHO as it is an important unmet medical need. To support this effort, WHO’s Product Development for Vaccines Advisory Committee (PDVAC) called for the development of a WHO preferred Product Characteristics (PPC) for new TB vaccines. PPCs describe WHO preferences for parameters of vaccines, in particular their indications, target groups, possible immunization strategies, and features of desired clinical data related to safety and efficacy, supportive of policy decision making. The primary target audience for the PPC is any entity intending to eventually seek WHO policy recommendations and prequalification for their products, which is required for procurement by UN agencies. Vaccine PPCs are built through a wide consensus building process and result from interactions with a variety of stakeholders.
The TB vaccine candidate pipeline includes various vaccine platforms including whole cell vaccines, adjuvanted proteins, and recombinant subunit vector vaccines. Candidate vaccines are being developed for prevention of TB disease in adolescents and adults, for early life immunization as BCG replacement, as BCG boosters, for vaccination of TB patients after treatment to prevent disease recurrence, or as immunotherapeutic adjuncts to drug therapy intended to reduce treatment duration. Up to recently, there was no coherently communicated consensus as to the preferred product characteristics (PPC) that would adequately support favorable policy recommendations for implementation where needed.
A WHO PPC document for new tuberculosis vaccines was developed to highlight the priority need for vaccines that protect against pulmonary TB in adults, and new TB vaccines with better safety and efficacy characteristic than BCG to administer to neonates and infants.
A WHO PPC document for tuberculosis vaccines for improvement of treatment outcome was also developed, more recently. Treating TB requires a multidrug course of treatment lasting 6 months, or longer for drug-resistant TB. Treatment failure and recurrence after end-of-treatment can have devastating consequences, and may be associated with the development of drug-resistant TB. Vaccines have the potential to serve as immunotherapeutic adjuncts to antibiotic treatment regimens for TB. A therapeutic vaccine for TB patients, administered towards completion of a prescribed course of drug therapy or at certain time(s) during treatment, could improve outcomes through immune-mediated control and clearance of bacteria and prevention of re-infection, and provide on the long-term options to simplify and shorten drug treatment regimen.
M72/AS01E candidate vaccine
Recently, an investigational TB vaccine candidate (M72/AS01E) was found to be significantly protective against TB disease in a Phase IIb trial conducted in Kenya, South Africa and Zambia, in individuals with evidence of latent tuberculosis infection. The point estimate of vaccine efficacy was 50% (90% CI, 12-71), over approximately three years of follow-up (see below for more information).
This result, unprecedented in decades of TB vaccine research in terms of clinical significance and strength of evidence, constitutes an important scientific breakthrough. In view of this public health opportunity, WHO engaged key stakeholders and the tuberculosis vaccine community to discuss future development options for this vaccine candidate. Reports from these consultations can be found below.
5 April 2019, Geneva, Switzerland
WHO also convened in Geneva a meeting to generate consensus on the clinical development pathway for the M72/AS01E TB vaccine candidate developed by GSK.
30-31 July 2019, Geneva, Switzerland
An investment case for new tuberculosis vaccines
WHO-commissioned a full value assessment for new TB vaccines to provide early evidence for national and global decision-makers involved in TB vaccine development and implementation, who include stakeholders involved in vaccine research, financing, regulation and policy-making, manufacturing, introduction and procurement. The report showcases the impact of novel TB vaccines on health, productivity, equity, antibiotic stewardship, cost–effectiveness and economic growth.
Clinical pipeline of new TB vaccines
WHO reports progress in the clinical development of new TB vaccines, in its annual Global TB Report and TB research tracker.
TB vaccine accelerator council
WHO’s Director-General established a TB vaccine accelerator Council in 2023 to facilitate the development, testing, authorization, and use of new TB vaccines, drawing on lessons learned from the response to the COVID-19 pandemic.
The Council is anticipated to work in multiple ways. These include
identifying needs for, and types of innovative sustainable financial solutions, as well as partnerships between the public, private and philanthropic sectors that can expedite the translation of science into TB vaccines, and ensure their equitable access once available;
identifying market solutions to incentivize TB vaccine development, and to ensure that the R&D ecosystem is positioned to rapidly manufacture and distribute vaccines equitably and at scale, once they are available; and
advocating with decision makers in the public, private, philanthropy and other relevant sectors to strengthen commitment and concerted action to develop and expand access to novel effective TB vaccines, including through political platforms such as the African Union, ASEAN, BRICS, G20, G7 and others.
Other resources
- WHO End TB Strategy
- TB vaccine accelerator council
- Global roadmap for research and development of tuberculosis vaccines
- Global strategy for TB research and innovation
- WHO TB research tracker
- Political declaration of the United Nations General Assembly High Level Meeting on TB
- Moscow Declaration to End TB
- Global tuberculosis report
- Global investments in tuberculosis research and development: past, present and future
- Tuberculosis Research Funding Trends
Contact
WHO’s work on new TB vaccines is being coordinated by the Immunization, Vaccines and Biologicals department (IVB) and the Global TB Programme (GTB)
For general inquiries, please contact: TBvaccines@who.int