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

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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