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Tuberculosis Vaccine Development in Denmark

Tuberculosis Vaccine Development in Denmark. Joshua Woodworth Post Doctoral Fellow Marie Curie IIF Statens Serum Institut Copenhagen , Denmark. About Me…. - From Detroit, MI - B.S. in Biology, University of Michigan - PhD in Immunology, Harvard Medical School

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Tuberculosis Vaccine Development in Denmark

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  1. Tuberculosis Vaccine Developmentin Denmark Joshua Woodworth Post Doctoral Fellow Marie Curie IIF StatensSerum Institut Copenhagen, Denmark

  2. About Me… • - From Detroit, MI • - B.S. in Biology, University of Michigan • - PhD in Immunology, Harvard Medical School • “T cell immune response to Tuberculosis Infection” • - Post Doc, TB Vaccine Development • Statens Serum Institut • Copenhagen, Denmark

  3. StatenSerum Institut (SSI)Copenhagen, Denmark • •       • Governmental Institute • Epidemiology • Medical sample Testing • Academics and Industry • Vaccine Development • HIV,TB, Malaria, Chlamydia, Strep A • Polio vaccine, BCG (TB vaccine) • Diagnostics • TB skin test (tuberculin)

  4. Tuberculosis is global health problem • 1/3 World Population latently infected • 8 million new TB cases annually • 1.5 million TB deaths annually • TB is the major cause of death of people with HIV/AIDS

  5. Tuberculosis Disease and Immunity T Cells CD4/CD8 Chemokines Reactivation Tuberculosis (5%) latency Inhalation of aerosolized M. tuberculosis Control of Infection (95%) Infection of Lung Alveolar Macrophages Primary Tuberculosis (~5% within 5 years)

  6. Vaccination against TB LATENT PHASE REACTIVATION ACUTE PHASE PHASE load 5 - 10% Bacterial 90 - 95% Disease Threshold Infection TIME Prophylactic Vaccination

  7. History of TB and Vaccines Development of current TB vaccine (BCG) 1921 Discovery of M.tuberculosis 1882

  8. Efficacy >80% Efficacy <20% <10 10-24 25-49 50-99 Rate per 100 thousand 100-249 250+ BCG is not effective against adult pulmonary TB

  9. TB vaccines currently in clinical trials EU SSI SSI SSI SSI Ottenhoff THM, Kaufmann SHE. (2012)PLoS Pathogens

  10. What’smissingfrom BCG? • Identification of key missing proteins • ESAT-6 (SSI) • TB Patients have immune responses to ESAT-6 • ESAT-6 is a virulence factor • Adding ESAT-6 back to BCG makes it more dangerous • (Pasteur Institute, Paris) Mtb BCG Harboe et al, IAI, 1996

  11. Vaccination with ESAT-6 protects from TB ESAT-6 D15ESAT-6 Non-Vaccinated X + ESAT-6 Adjuvant (CAF01) Lung Bacteria

  12. T cells target only one ‘epitope’ of ESAT-6 ESAT-6 D15ESAT-6 Non-Vaccinated X + T cell response ESAT-6 Adjuvant (CAF01) Lung Bacteria

  13. T cell responses against cryptic epitopes of ESAT-6 give protection ESAT-6 D15ESAT-6 Non-Vaccinated X T cell response Lung Bacteria

  14. T cell responses against cryptic epitopes of ESAT-6 give protection ESAT-6 D15ESAT-6 Non-Vaccinated X T cell response Lung Bacteria

  15. T cell responses against cryptic epitopes have improved functional profile ESAT-6 D15ESAT-6 Non-Vaccinated X T cell response T cell ‘exhaustion’

  16. T cell responses against cryptic epitopes have improved functional profile ESAT-6 D15ESAT-6 Non-Vaccinated X T cell response Look less like TB-driven T cells (which are associated with disease)

  17. load 5 - 10% Bacterial 90 - 95% Disease Threshold Infection TIME Post-infection Prophylactic Vaccination Vaccination

  18. WhyEurope? • Science is science everywhere • Strong research and technology an innovation environment • Collaborative research projects • Shared knowledge and tools • Build professional network

  19. Consortiums and Collaborative ResearchProjects • Local Collaborations • Copenhagen University • Danish Technical University • Herlev Hospital • Hvidovre Hospital • EU Projects • NEW TB VACC • - Max Plank, PasteurInst, GSK, Leiden Univ MC, more… • GENIVAC • CENTER FOR NANOVACCINES • SAFEVAC • International Collaborations • US, South Africa, India

  20. WhyEurope? Meetings

  21. WhyEurope? Meetings Personal Travel I grew up in Europe, where history comes from. - Eddie Izzard

  22. Work and life in Denmark… `

  23. Themes to include • •       Europe has a vibrant and attractive science, technology and innovation culture; • •       Europe provides opportunities for career development and advancement; • •       Europe's industry and research organizations offer challenging opportunities to work in world-class environments.

  24. + + ACUTE PHASE PROTEIN REACTIVATION PHASE PROTEIN LATENT PHASE PROTEIN load 5 - 10% Bacterial 90 - 95% Disease Threshold Infection TIME Post-infection Prophylactic Vaccination Vaccination

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