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Vaccine Development
Gerald R. Kovacs, Ph.D.Scientific Director
Advanced BioScience LaboratoriesMaryland, USA
Vaccines work by mimicking disease agents and stimulating the immune system to build up defenses
against them
Vaccine design and development
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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
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Antigen presentation
T-helper cell
Killer T cell
B cell: antibodies(neutralize & bridge)
Antigen presentation
•Non-infectious vaccines
•Live attenuated virus•Carrier vaccines•DNA vaccines
…By inducing adaptive immunity & memory!
How do vaccines work?
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Vaccine Development
Agent Antigen ID Vaccine Candidate
Vaccine Characteri
zationPreclinical
GMP Manufact
urePhase 1 Phase 2 Phase 3
Safety
Pivotal Animal Efficacy
Animal Efficacy Model Development
Phase 4
Proof of ConceptFeasibility
FormulationIdentityPurity
StabilityRisk Assessments
PotencyToxicology
DosageSchedule
Mech. of ActionMarkersAdjuvant
GMP ProductionGLP ToxicologyGCP EvaluationQuality Control
Quality AssuranceRegulatory Affairs
IND BLAEUA
3-7 years 1-2 years 5-10 years
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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
57% 41% 32% 23% 18.4%
Probability of Success in Transition
Vaccine Development Timeline
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1967. FluMist concept published in Nature
1991. Developed with NIAID support and licensed to Wyeth
1995. Licensed to Aviron.
2003. Approved for use.
From idea to approval can take decades and $100s of millions.
Effective vaccines for many diseases (HIV, Malaria) elusive after substantial investment of resources
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EBOLA VIRUS VACCINES
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Ebola Vaccines in DevelopmentPreclinical Phase 1 Phase 2 Phase 3
Profectus VSV
Inovio DNA
Mapp BioP ZMapp
Vaxart Oral
GSK ChAd3
Merck ∆G-VSV
GSK ChAd3,Merck VSV,
Placebo
J&J/Bavarian Nordic P/B
GSK ChAd3
NovaVax VLP
Bavarian Nordic MVA
Discovery
Novartis RNA
Protein Sciences subunit
USAMRIID replicons and VLPs
TJU Attenuated rabies vector
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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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THANK YOU