Advanced BioScience Laboratories Vaccine Development Gerald R. Kovacs, Ph.D. Scientific Director Advanced BioScience Laboratories Maryland, USA

Vaccine design and development Vaccines work by mimicking disease agents and stimulating the immune system to build up defenses against them 2

History of Vaccines 1798 - Edward Jenner noted: Smallpox and Cowpox: Milkmaids frequently contracted cowpox which caused lesions similar to that smallpox Milkmaids who had cowpox almost never got smallpox Jenner’s experiment: Collected pus from cowpox sores Injected cowpox pus into boy named James Phipps Then injected Phipps with pus from smallpox sores Phipps did not contract smallpox First to introduce large scale, systematic immunization against smallpox 3

How do vaccines work? Live attenuated virus Carrier vaccines DNA vaccines Antigen presentation T-helper cell Antigen presentation Killer T cell Non-infectious vaccines B cell: antibodies (neutralize & bridge) …By inducing adaptive immunity & memory! 4

Vaccine Development IND EUA BLA 3-7 years 1-2 years 5-10 years Agent Antigen ID Vaccine Candidate Vaccine Characterization Preclinical GMP Manufacture Phase 1 Phase 2 Phase 3 Safety Phase 4 Animal Efficacy Model Development Pivotal Animal Efficacy Proof of Concept Feasibility Formulation Identity Purity Stability Risk Assessments Potency Toxicology Dosage Schedule Mech. of Action Markers Adjuvant GMP Production GLP Toxicology GCP Evaluation Quality Control Quality Assurance Regulatory Affairs 3-7 years 1-2 years 5-10 years

Probability of Success in Transition Probability of transition between each phase of development 57% 72% 71% 80% 79% Pre-Clinical Phase 1 Phase 2 Phase 3 BLA Market Cumulative probability of success through each phase 41% 32% 23% 18.4% 6

Vaccine Development Timeline From idea to approval can take decades and $100s of millions. 1967. FluMist concept published in Nature 1991. Developed with NIAID support and licensed to Wyeth 1995. Licensed to Aviron. 2003. Approved for use. Effective vaccines for many diseases (HIV, Malaria) elusive after substantial investment of resources

Ebola virus vaccines

Ebola Vaccines in Development Discovery Preclinical Phase 1 Phase 2 Phase 3 USAMRIID replicons and VLPs Bavarian Nordic MVA GSK ChAd3 GSK ChAd3 GSK ChAd3, Merck VSV, Placebo Protein Sciences subunit Profectus VSV Merck ∆G-VSV Novartis RNA Inovio DNA J&J/Bavarian Nordic P/B Vaxart Oral NovaVax VLP TJU Attenuated rabies vector Mapp BioP ZMapp

Emerging and Re-emerging Infectious Diseases

Future of Vaccines Public-Private Partnerships Continued research on host-pathogen responses Innovation and rational design of vaccines Use of systems biology Rapid and flexible production platforms Effective regulatory pathways Long term federal and private industry support

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