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

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

3. 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

4. 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

5. 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

6. 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

7. 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

8. Ebola virus vaccines

9. 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

10. Emerging and Re-emerging Infectious Diseases

11. 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

12. Thank You