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
To develop new, more effective vaccines that will directly and safely prevent TB in all age groups and populations
- 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
● 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.
|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|