Research and Innovation Research and Innovation Tuberculosis Vaccine Development in Denmark Joshua Woodworth Post Doctoral Fellow Marie Curie IIF Statens Serum Institut Copenhagen, Denmark

Policy Research and Innovation Research and Innovation 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

Policy Research and Innovation Research and Innovation Staten Serum 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)

Policy Research and Innovation Research and Innovation 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 Tuberculosis is global health problem

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

Policy Research and Innovation Research and Innovation TIME ACUTE PHASE LATENT PHASE REACTIVATION PHASE Bacterial load 90-95% 5-10% Prophylactic Vaccination Disease Threshold Infection Vaccination against TB

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

Policy Research and Innovation Research and Innovation BCG is not effective against adult pulmonary TB Rate per 100 thousand < Efficacy >80% Efficacy <20%

Policy Research and Innovation Research and Innovation TB vaccines currently in clinical trials Ottenhoff THM, Kaufmann SHE. (2012) PLoS Pathogens EU SSI

Policy Research and Innovation Research and Innovation Whats missing from BCG? Harboe et al, IAI, 1996 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) BCGMtb

Policy Research and Innovation Research and Innovation Vaccination with ESAT-6 protects from TB Non-Vaccinated ESAT-6 15ESAT-6 X + ESAT-6Adjuvant (CAF01) Lung Bacteria

Policy Research and Innovation Research and Innovation T cells target only one epitope of ESAT-6 Non-Vaccinated ESAT-6 15ESAT-6 X + ESAT-6Adjuvant (CAF01) T cell response Lung Bacteria

Policy Research and Innovation Research and Innovation T cell responses against cryptic epitopes of ESAT-6 give protection Non-Vaccinated ESAT-6 15ESAT-6 X T cell response Lung Bacteria

Policy Research and Innovation Research and Innovation T cell responses against cryptic epitopes of ESAT-6 give protection Non-Vaccinated ESAT-6 15ESAT-6 X T cell response Lung Bacteria

Policy Research and Innovation Research and Innovation Non-Vaccinated ESAT-6 15ESAT-6 X T cell responses against cryptic epitopes have improved functional profile T cell exhaustion T cell response

Policy Research and Innovation Research and Innovation Non-Vaccinated ESAT-6 15ESAT-6 X T cell responses against cryptic epitopes have improved functional profile T cell response Look less like TB-driven T cells (which are associated with disease)

Policy Research and Innovation Research and Innovation TIME Bacterial load 90-95% 5-10% Prophylactic Vaccination Disease Threshold Infection Post-infection Vaccination

Policy Research and Innovation Research and Innovation Why Europe? Science is science everywhere Strong research and technology an innovation environment Collaborative research projects Shared knowledge and tools Build professional network

Policy Research and Innovation Research and Innovation Consortiums and Collaborative Research Projects Local Collaborations Copenhagen University Danish Technical University Herlev Hospital Hvidovre Hospital EU Projects NEW TB VACC - Max Plank, Pasteur Inst, GSK, Leiden Univ MC, more… GENIVAC CENTER FOR NANOVACCINES SAFEVAC International Collaborations US, South Africa, India

Policy Research and Innovation Research and Innovation Meetings Why Europe?

Policy Research and Innovation Research and Innovation Why Europe? I grew up in Europe, where history comes from. - Eddie Izzard Meetings Personal Travel

Policy Research and Innovation Research and Innovation ` Work and life in Denmark…

Policy Research and Innovation Research and Innovation

Policy Research and Innovation Research and Innovation 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.

Policy Research and Innovation Research and Innovation TIME ACUTE PHASE PROTEIN LATENT PHASE PROTEIN REACTIVATION PHASE PROTEIN Bacterial load 90-95% 5-10% Prophylactic Vaccination Disease Threshold Infection Post-infection Vaccination + +