Strategic Framework

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.

ObjectiveMilestone(s)Major ActivitiesFunding Required 2018–2022 (US$ millions)
Continue to advance the clinical pipeline of TB vaccine candidatesAdvance candidate and candidate concepts through clinical trials, utilizing portfolio management and common stage-gating criteriaInitiate Phase III trial of M72/AS01E vaccine candidate1250
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 resourcesConduct trials using prevention of infection and prevention of recurrence study designs75
Ensure sufficient capacity to support large-scale clinical trials Scale up manufacturing to support large-scale (Phase IIb/III) clinical trials500
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 trialsConduct incidence and prevalence of TB infection studies; incidence of disease studies; and cross-sectional prevalence of disease studies in multiple regions25
Total Objective 1 – Clinical pipeline1850
Enhance knowledge through experimental medicineDevelop and test a human challenge model to speed TB vaccine R&DSupport consortium to advance human challenge model through development and preclinical phase, and initiate clinical phase40
Complete human studies in parallel with NHP challenge in order to learn about protective immune responsesConduct NHP challenge studies to determine correlates of protective immunity150
Compare results from these NHP studies with those in human efficacy trials (and back- translation for model verification)
Test key hypotheses about protective immune responsesConduct multiple experimental medicine studies to test different hypotheses100
Total Objective 2 – Experimental medicine290
Increase emphasis on early-stage and discovery researchIdentify immune correlates of protection and diseaseIdentify immune mechanisms and correlates, through preclinical comprehensive host response analysis60
Integrate biomarker discovery into all Phase IIb and Phase III studies100
Identify novel vaccine targetsExplore 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 research300
Improve animal modelsDevelop 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 models150
Improve preclinical and clinical readoutsStandardize reagents and harmonize assays and benchmark relevant signals by forward - as well as backward -translation / verification between preclinic and clinicStudies of cost-of goods, TB cost–effectiveness, full value proposition, health-economic assessment, country vaccine readiness, and vaccine landscape12
Continue and expand on programmes to provide reagents to laboratories and research facilities30
Develop necessary assays based on stakeholder consensus40
Total Objective 5 – Reagents and assays71
Lay the groundwork for adolescent and adult vaccination campaignsConduct strategic access and implementation research, including studies of cost-of goods, TB cost–effectiveness, country vaccine readiness, and vaccine landscape12
Total Objective 6 – Conduct strategic access research12
Engage communities in TB vaccine R&DStrengthen community engagement in researchClinical trials have community advisory/ engagement plans and involve community representatives in the design, conduct and dissemination of research90
Vaccine developers actively engage community stakeholders in the R&D process, from early- stage research to clinical trials and licensure
Total Objective 7 – Community engagement90
Grand Total2763