Tuberculosis Vaccines: A strategic blueprint for the next decade

1. Tuberculosis Vaccines: A strategic blueprint for the next decade Co-editors: Michael J. Brennan and Jelle Thole

2. The Global Burden of TB -2010 Estimated number of cases Estimated number of deaths 8.8 million (range: 8.5–9.2 million) 1.45 million (range: 1.2–1.6 million) All forms of TB HIV-associated TB 1.1 million (13%) (range: 1.0–1.2 million) 350,000 (range: 320,000–390,000) 440,000 (range: 390,000–510,000) about 150,000 Multidrug-resistant TB (MDR-TB) 1/3 of the global population (2 billion) is estimated to be latently infected with TB and at risk of developing the disease later in life

3. 10000 1000 TB incidence 10x lower than today, but >100x higher than elimination target in 2050 Incidence/million/yr 100 10 Elimination 16%/yr Elimination target: 1 / million / year by 2050 Global Plan 6%/yr Current trajectory 1%/yr 1 2000 2010 2020 2030 2040 2050 Year Full implementation of Global Plan: 2015 MDG target reached but TB not eliminated by 2050 Current rate of decline

4. Predicted impact of new TB vaccine Young and Dye. 2006. Cell 124:683-7 L. Abu Raddadet al, PNAS 2009

5. Why new TB vaccines • Calmette & Guérin developed the only available TB vaccine: BCG (1906-1921) • BCG reduces risk of severe pediatric TB disease - 40 thousand cases per year • Protection against adult pulmonary TB, which accounts for most TB worldwide, is poor or variable at best • Not known to protect against latent infection or prevent reactivation • High risk of disseminated BCG in HIV positive infants

6. Global TB vaccine pipeline: 12 in clinical trials Stop-TB partnership TB vaccine candidates 2009

7. Why a strategic Blueprint? • Outline the major challenges and key issues for the next decade and communicate them to broader audience • Build consensus on key issues • Demonstrate a coordinated approach to TB vaccine development • Use key challenges and questions in Blueprint as a rallying point for forming new partnerships • Use issues outlined in Blueprint for soliciting specific funding from donors.

8. History of TB Vaccine Development Past Decade of Progress Blueprint I 1998 Global Forum I Geneva 2001 No new preventive TB vaccines in clinical trials 1st preventive vaccine enters clinical trials (MVA85A) 1st Phase IIb proof-of-concept of preventive vaccine initiated 15 vaccines studied in clinical trials, 12 were in clinical trials 2000 202 2009 2011 Next Decade of Progress Annecy “Out of Box” Vancouver, Keystone TB Les Diablerets, TBVAC Advocacy StopTB WG Blueprint II March 2012 Global Forum III Cape Town, 2013 Global Forum II Estonia 2010 2011 2012 2013 to 2020 Phase III trials of preventive vaccines One new TB vaccine introduced Correlate of vaccine immunity established Novel vaccines for all populations developed Resources obtained that match need

9. Tuberculosis Vaccines: A Strategic Blueprint for the Next Decade • A unified global strategy • Renewed, intensified and well integrated international effort • Outlining major scientific challenges, critical activities and crucial questions

10. 5 priority areas / 14 critical activities • Creativity in research and discovery • Correlates of Immunity and Biomarkers for TB Vaccines • Clinical Trials – Harmonisation and Cooperation • Rational Selection of TB Vaccine Candidates • Building Support through Advocacy, Communications and Resource Mobilisation

11. Creativity in Research and Discovery • Identify mechanisms of protective immunity • Introduce new vaccine mechanisms • Facilitate translational research, comparative preclinical studies and animal models

12. Correlates of Immunity and Biomarkers for TB Vaccines • Explore novel approaches to identify correlates of immunity • Introduce novel assays in efficacy trials to help establish correlates of immunity. • Identify signatures of vaccine efficacy

13. Clinical trials: harmonization & cooperation • Determine TB prevalence and incidence, select trial sites and choose target populations • Design clinical trials to determine efficacy using better defined clinical endpoints • Address regulatory, ethical and sustainability issues

14. Rational selection of TB vaccine candidates • Establish global criteria for assessing vaccine candidates in clinical studies • Obtain consensus on criteria to advance new candidates

15. Building support through advocacy, communications & resource mobilization • Expand financing • Raise awareness and build support for the role of new TB vaccines • Broaden the base of TB vaccine advocates

16. Implementing the Blueprint March 20th – Journal Publication Date and Launch Global Press Release from Working Group, Aeras, TBVI Adapted press releases for South Africa and other partners also on March 20 Johannesburg Press Briefing, March 20th March 20th/21st – Congressional briefings in Washington, DC March 22nd – TBVI Event in Brussels Companion piece developed for distribution to broader audiences 3rdFlobal Forum on TB Vaccines (March 2013, Cape Town) structured to address key challenges in Blueprint (www.tbvaccine2013.org)

17. Thanks We are particularly grateful to all the researchers, clinicians, pharmaceutical companies, governmental and non-governmental organizations, donors and other stakeholders who completed survey questions that helped define the key priorities in TB vaccine development and to those who participated in spirited discussions at the TB blueprint meetings held in 2010 and 2011. The following who contributed directly to the content of the Blueprint. Erna Balk, TBVI, Lelystad, The Netherlands Lewellys Barker, Aeras, Rockville, United States of America Jerrold Ellner, Boston University and Boston Medical Center Boston, USA Bernard Fourie, University of Pretoria, Pretoria, South Africa Luc Hessel, TBVI, Lelystad, The Netherlands Stefan Kaufmann, Max Planck Institute for Infection Biology, Berlin, Germany Melody Kennell, Aeras, Rockville, United States of America Hassan Mahomed, University of Cape Town, Cape Town, South Africa Tom Ottenhoff, Leiden University Medical School, Leiden, The Netherlands Joris Vandeputte, TBVI, Lelystad, The Netherlands Barry Walker, National Institute for Biological Standards and Control, Potters Bar, UK Jennifer Woolley, Aeras, Rockville, United States of America

18. Thanks The Blueprint was coordinated by the Stop TB Partnership Working Group on New TB Vaccines with support from the World Health Organization, Bill & Melinda Gates Foundation, Aeras, TuBerculosis Vaccine Initiative, and the EC FP 7 framework programme. Members of the Stop TB Partnership Working Group on New TB Vaccines Leadership Team Michel Greco, Chair Ulrich Fruth, WHO & Jennifer Woolley, Aeras, Secretarat Michael Brennan, Aeras Jelle Thole, TBVI Hassan Mahomed, SATVI Susanne Verver, KNCV Peggy Johnston, Jan Gheuens, Peter Small, Bill & Melinda Gates Fdn Christine Sizemore, NIAID, NIH Robert Nakibumba, Community Representative, Working Group on New TB Vaccines TASO Uganda Lucy Ghati, The National Empowerment Network of People Living with HIV/AIDS (NEPHAK), Kenya Christian Lienhardt, StopTB Partnership Dave Lewinsohn, Oregon Health and Sciences University Didier Lapierre, GSK Biologicals