The Global Plan to End TB 2018-2022 lays out a strategic framework for TB vaccines through the end of the decade.
This framework is guided by the following priority actions for TB vaccine R&D:
- Accelerate the late-stage development of vaccine candidates, including late-stage evaluation of the M72/AS01E vaccine candidate, and work with countries to prepare for successful licensure and roll-out.
- Accelerate the development of next-generation vaccine candidates to ensure highly effective vaccines for all affected populations.
- Evaluate novel TB vaccine concepts and investigate mechanisms and correlates of vaccine-induced protection
Priority actions in the following areas will also be necessary to advance TB research and the development of new tools, including vaccines:
- Invest in basic science research
- Create an enabling environment for TB R&D
- Optimize access to new tools
- Advocate effectively and strengthen community systems
- Include advocates and members of TB affected communities in decision-making structures and scientific forums.
New Vaccines Strategic Framework 2018–2022
Vision:
To develop new, more effective vaccines that will directly and safely prevent TB in all age groups and populations
Goals:
- Prevent TB disease and interrupt transmission through the development of new vaccines that would prevent infection, reactivation or reinfection
- Incorporate and consider access strategies throughout the TB vaccine development process
- Strengthen community engagement in TB vaccine R&D.
| Objective | Milestone(s) | Major Activities | Funding Required 2018–2022 (US$ millions) |
|---|---|---|---|
| Continue to advance the clinical pipeline of TB vaccine candidates | Advance candidate and candidate concepts through clinical trials, utilizing portfolio management and common stage-gating criteria | Initiate Phase III trial of M72/AS01E vaccine candidate | 1250 |
| Continue to support vaccine Continue to support vaccine candidates through the clinical pipeline and initiate new Phase I/IIa/IIb trials on vaccine candidates that meet criteria | |||
| Explore and implement novel Phase II clinical trial designs to identify the most promising vaccines as early as possible in development and optimize use of resources | Conduct trials using prevention of infection and prevention of recurrence study designs | 75 | |
| Ensure sufficient capacity to support large-scale clinical trials | Scale up manufacturing to support large-scale (Phase IIb/III) clinical trials | 500 | |
| Expand clinical trial Expand clinical trial and laboratory capacity in different regions to conduct clinical trials at GCP standards | |||
| Conduct studies to assess prevalence and incidence of relevant TB vaccine trial endpoints in populations to be involved in clinical efficacy trials | Conduct incidence and prevalence of TB infection studies; incidence of disease studies; and cross-sectional prevalence of disease studies in multiple regions | 25 | |
| Total Objective 1 – Clinical pipeline | 1850 | ||
| Enhance knowledge through experimental medicine | Develop and test a human challenge model to speed TB vaccine R&D | Support consortium to advance human challenge model through development and preclinical phase, and initiate clinical phase | 40 |
| Complete human studies in parallel with NHP challenge in order to learn about protective immune responses | Conduct NHP challenge studies to determine correlates of protective immunity | 150 | |
| Compare results from these NHP studies with those in human efficacy trials (and back- translation for model verification) | |||
| Test key hypotheses about protective immune responses | Conduct multiple experimental medicine studies to test different hypotheses | 100 | |
| Total Objective 2 – Experimental medicine | 290 | ||
| Increase emphasis on early-stage and discovery research | Identify immune correlates of protection and disease | Identify immune mechanisms and correlates, through preclinical comprehensive host response analysis | 60 |
| Integrate biomarker discovery into all Phase IIb and Phase III studies | 100 | ||
| Identify novel vaccine targets | Explore different mechanisms of protective immunity (e.g. mucosal, alternate cellular targets, innate immunity, and humoral immunity) | 40 | |
| Investigate new approaches to mount an effective response | ● Conduct studies of
unconventional
immune cells ● Conduct studies of humoral immunity ● Improve formulation and antigen delivery, through adjuvant and vector development (Note: robust and scalable). ● More optimal delivery, e.g. through exploring unconventional routes of vaccine delivery. | 100 | |
| Total Objective 3 – Early-stage and discovery research | 300 | ||
| Improve animal models | Develop and optimize fit for purpose animal models, to also allow assessment of vaccine efficacy in immunologically primed and/or latently infected individuals or under conditions of coinfection or comorbidity, to find signals of prevention of infection and/or recurrence of disease or blockade of natural transmission. | Enhance infrastructure and diversity the portfolio of modalities for preclinical stage and priority gating of candidates; qualify and verify models by benchmarking against clinical signals. | 150 |
| Total Objective 4 – Animal models | 150 | ||
| Improve preclinical and clinical readouts | Standardize reagents and harmonize assays and benchmark relevant signals by forward - as well as backward -translation / verification between preclinic and clinic | Studies of cost-of goods, TB cost–effectiveness, full value proposition, health-economic assessment, country vaccine readiness, and vaccine landscape | 12 |
| Continue and expand on programmes to provide reagents to laboratories and research facilities | 30 | ||
| Develop necessary assays based on stakeholder consensus | 40 | ||
| Total Objective 5 – Reagents and assays | 71 | ||
| Lay the groundwork for adolescent and adult vaccination campaigns | Conduct strategic access and implementation research, including studies of cost-of goods, TB cost–effectiveness, country vaccine readiness, and vaccine landscape | 12 | |
| Total Objective 6 – Conduct strategic access research | 12 | ||
| Engage communities in TB vaccine R&D | Strengthen community engagement in research | Clinical trials have community advisory/ engagement plans and involve community representatives in the design, conduct and dissemination of research | 90 |
| Vaccine developers actively engage community stakeholders in the R&D process, from early- stage research to clinical trials and licensure | |||
| Total Objective 7 – Community engagement | 90 | ||
| Grand Total | 2763 | ||