Dr. Bob Nordgren - Mucosal Vaccination Principles & Practices
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Mucosal Vaccination Principles & Practices - Dr. Bob Nordgren, Aptimmune, from the 2018 Aptimmune Pre-AASV Symposium, March 2, 2018, San Diego, CA, USA. More presentations at http://www.swinecast.com/2018-aptimmune-symposium-aasv
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Dr. Bob Nordgren - Mucosal Vaccination Principles & Practices
- 1. MucosalVaccination Principals & Practices Dr. Bob Nordgren, Aptimmune
- 3. Protective immunogens Classical fractionated NewTech Rec subunit NewTech VLPs NewTech * VectoredVacc. NewTech DNAVacc. The Bug Virus Bacterium * Different categories of vectored vaccines Gene Deleted live
- 4. Protective immunogens Classical fractionated NewTech Rec subunit NewTech VLPs NewTech * VectoredVacc. NewTech DNAVacc. The Bug Virus Bacterium * Different categories of vectored vaccines Veterinary vaccines Gene Deleted live
- 5. Those who ignore history have no past and no future.
- 6. Vaccine Production: FMD IFFA (1974) The use of Bovine tongue epithelium to produce FMD vaccines (Frenkel’s method)
- 7. The era of industrial biology From tongue epithelium to cell culture in biogenerators Vaccine Production: FMD
- 8. The era of convergence biology Baculovirus produced in silkworm larvae Vaccine Production: FMD
- 9. Advanced EnablingTechnologies (AET’s) To provide efficacy in the face of MDA (CPV, FPL)
- 10. Advanced EnablingTechnologies (AET’s) To provide efficacy in the face of MDA (CPV, FPL) To improve the safety of classical vaccines (FeLV, FR)
- 11. Advanced EnablingTechnologies (AET’s) To provide efficacy in the face of MDA (CPV, FPL) To improve the safety of classical vaccines (FeLV, FR) To develop marker vaccines (DIVA, PRV)
- 12. Advanced EnablingTechnologies (AET’s) To provide efficacy in the face of MDA (CPV, FPL) To improve the safety of classical vaccines (FeLV, FR) To develop marker vaccines (DIVA, PRV) To target diseases for which a classical approach offers no solution (chronic infections, cancer, parasites)
- 13. Advanced EnablingTechnologies (AET’s) To provide efficacy in the face of MDA (CPV, FPL) To improve the safety of classical vaccines (FeLV, FR) To develop marker vaccines (DIVA, PRV) To target diseases for which a classical approach offers no solution (chronic infections, cancer, parasites) For rapid solutions against emerging diseases (Avian influenza, AHS)
- 14. Advanced EnablingTechnologies (AET’s) To provide efficacy in the face of MDA (CPV, FPL) To improve the safety of classical vaccines (FeLV, FR) To develop marker vaccines (DIVA, PRV) To target diseases for which a classical approach offers no solution (chronic infections, cancer, parasites) For rapid solutions against emerging diseases (Avian influenza, AHS) Improved routes of administration – uptake (In Ovo, Transdermal, Intranasal)
- 15. Down to Basics
- 20. Preferential Uptake of Nanoparticle- Antigen Complex Virus control rticles engulfed by alveolar hs of PLGA [poly (DL-lactide-co- (c) (d) Nanoparticle-PRRSVAgs Killed-PRRSVAgs PRRSV Uptake by ZMAC 20 Aptimmune’s vaccine delivers antigen to immune cells comparable to live virus without inducing cell death. [Dwivedi and Renukaradhya (2012, PLoS One); Renukaradhya et al. (2015)]
- 23. AttitudeSymptoms 23 CD4+ Th1 ,Th2 CTL+ TNF-ɑ, INF IgG SIgA
- 24. Broadly reactive Ig’s 24 Broadly reactive IgA
- 27. PRRSV IgA Detected in Bronchoalveolar Lavage Fluids Testing of BAL 14- days post-challenge - PRRSV IgA levels in vaccine Formulas A and B are increased. Formula B significantly different than placebo. Formula A increased and with less variation. P la c e b o F o rm u la A F o rm u la B IM C o n tro l 0 .0 0 .5 1 .0 1 .5 Ig A in B A L ODvalue p = 0 .2 9 1 p = 0 .0 2 5 p = 0 .7 6 0
- 28. Systemic Antibody Response FormulaA and B Barricade mucosal vaccine induced post-challenge anamnestic response confirming immune response via intranasal administration Results detect circulating “systemic” antibody 7 days post challenge
- 29. BARRICADE™ Formulation Technology: POCStudy 0 20 40 60 80 100 Mock Vaccine Traditional Autogenous PRRSV IM BARRICADE™ PRRSV POC Formulation %ofpigswithvirusintheirlungs @21dpostchallenge Aptimmune’s BARRICADE™ FormulationTechnology provided superior virus clearance from lung versus mock & traditional autogenous PRRSV vaccines. 1.26x103 * 1.85x10 * 1.24x103 * * BAL = replicating virus titer for positive animals
- 30. Nanoparticle PRRSVVaccine Reduced the Lung Pathology Nanoparticle PRRSV vaccineKilled-PRRSV vaccine UnvaccinatedHealthy Control pig lung Two doses of Barricade PRRSV • Intranasal delivery • 1st Dose: 7-10 days of age • 2nd Dose: 21 days of age Heterologous PRRSV challenge
- 31. Any RespiratorySymptom 83% 83% 83% 83% 83% 42% 50%50% 50% 67% 50% 17% 33% 33% 17% 17% 25% 17% 8% 25% 33% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 7 8 9 10 11 12 13 Placebo IM Control Barricade PRRSV * * ** *Indicates statistical difference p>0.05 Days Post Challenge
- 32. Abdominal BreathingSymptoms 67% 67% 67% 58% 58% 33% 25% 33% 33% 67% 17% 17% 17% 17% 0% 0% 0% 8% 0% 17% 8% 0% 10% 20% 30% 40% 50% 60% 70% 80% 7 8 9 10 11 12 13 Placebo IM Control Barricade PRRSV * *** Days Post Challenge *Indicates statistical difference p>0.05