Tuberculosis Vaccine Development in Denmark Joshua Woodworth Post

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

About Me… • - From Detroit, MI • - B. S. in Biology, University of Michigan • - Ph. D 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

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

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 Policy Research and Innovation

Tuberculosis Disease and Immunity T Cells Chemokines CD 4/CD 8 Inhalation of aerosolized M. tuberculosis latency (5%) Control of Infection (95%) Infection of Lung Alveolar Macrophages Reactivation Tuberculosis Primary Tuberculosis (~5% within 5 years) Policy Research and Innovation

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

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

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

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

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

Vaccination with ESAT-6 protects from TB Non-Vaccinated ESAT-6 D 15 ESAT-6 X + ESAT-6 Lung Bacteria Policy Research and Innovation Adjuvant (CAF 01)

T cells target only one ‘epitope’ of ESAT-6 T cell response Non-Vaccinated D 15 ESAT-6 X + ESAT-6 Lung Bacteria Policy Research and Innovation Adjuvant (CAF 01)

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

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

T cell responses against cryptic epitopes have improved functional profile ESAT-6 T cell response Non-Vaccinated T cell ‘exhaustion’ Policy Research and Innovation D 15 ESAT-6 X

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

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

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

Meetings Why Europe? Policy Research and Innovation

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

Work and life in Denmark… ` Policy Research and Innovation

Policy 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

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