Brown University hosted a lecture on vaccine research and development given by Dr. Annie De Groot. The summary discusses:
1) It currently costs $200-500 million to develop a new vaccine, but the market has increased fivefold from 1990-2000 to $8 billion annually.
2) Vaccines work by training the immune system to recognize and fight infection without exposure to the pathogen. They include live attenuated, whole killed, subunit, and genetic vaccines.
3) Emerging infectious diseases since 1990 include hantavirus, ehrlichiosis, West Nile virus, SARS, and avian influenza. Preparedness for future pandemics requires vaccines for highly infectious pathogens.
Emixa Mendix Meetup 11 April 2024 about Mendix Native development
De Groot Nova Se Immunology Of Vaccines2009
1. Brown University University of Rhode Island and EpiVax, Providence RI January 2009 Annie De Groot MD Immunology of Vaccines
2. Outline Vaccine Research and Development Immunology of Vaccines Some Case Studies: tetanus smallpox polio Emerging infectious diseases Vaccine technology now
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4. Drug Development Process Laboratory R+D Pre-IND - Safety/Toxicity -> IND filing Phase I - human safety/toxicity Phase II - efficacy Phase III - extended studies / other drug(s) NDA -> FDA Approval Post-licensure surveillance
5. 2008 Success!: New HPV (Cervical Cancer) Vaccine almost 100% effective!
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9. Outline Vaccine Research and Development Immunology of Vaccines Some Case Studies: tetanus smallpox polio Emerging infectious diseases Vaccine technology now
10. What does a vaccine do? . . . Trains the immune system to recognize and fight infection . . . Without requiring exposure to the pathogen
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12. Basic Principles of Vaccine Immunology Innate immunity (e.g., macrophages, neutrophils, certain molecules) is the first line of defense. It is fast (usually good-to-go) and usually effective. Adaptive immunity (mediated by B and T cells) can be slow to respond (several days). It is highly effective when the innate immune system cannot fully deal with the threat.
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14. Primary response (primary immunization) is relatively: Secondary response (secondary immunization or booster immunization) is relatively: slow (4-7days) small amount of antibody (low concentration of antibody) low affinity antibody IgM first, IgG second (equal amounts of IgM and IgG) fast (2-4 day) large amounts of antibody high affinity antibody mostly IgG
16. Often, a secondary (memory) response is so fast and effective in removing antigens (pathogens), there are few or no symptoms detected by the infected individual (protective immunity). Secondary responses are the reason we do not get certain infectious diseases more than once. Secondary responses also explain why vaccinations work. For vaccinations, instead of immunizing with something that makes you sick, a vaccine contains antigens prime the immune response.
34. Outline Vaccine Research and Development Immunology of Vaccines Some Case Studies: tetanus smallpox polio Emerging infectious diseases Vaccine technology now
44. Outline Vaccine Research and Development Immunology of Vaccines Some Case Studies: tetanus smallpox polio Emerging infectious diseases Vaccine technology now
49. Outline Vaccine Research and Development Immunology of Vaccines Some Case Studies: tetanus smallpox polio Emerging infectious diseases Vaccine technology now
55. EpiVax: Accelerating Vaccines and Biologics Research and Development Anne S. De Groot 1, 2,3, L.Moise 1, 3 , J.A. McMurry 1 , W. Yang 1 , William Martin 1 1 EpiVax, Inc. 2 Brown Medical School and 3 University of Rhode Island [email_address] http://www.EpiVax.com
56. We think about what a vaccine does. . . . . . Trains the immune system to recognize and fight infection . . . Without requiring exposure to the pathogen using “epitopes” = chains of amino acids
57. Current Vaccine–Related NIH Funding 1R43AI058376 "A novel Smallpox Vaccine Derived from the VV/VAR Immunome“ 1R43AI065036 "A Genome-Derived, Epitope-Driven H pylori Vaccine“ 1R43AI058326 "A Genome-Derived, Epitope-Driven Tularemia Vaccine" 1R43AI075830-01 “ Optimization of a Multivalent Tuberculosis Vaccine” 7R01AI050528 (new R21: Optimization of HIV Vaccine Delivery) Epitope Driven HIV Vaccine Development Unfunded : Influenza, HPV, EBV
58. EpiVax Genome-derived, epitope-driven vaccine approach : In Silico EpiMatrix / ClustiMer / OptiMatrix [class I and class II alleles] Conservatrix / BlastiMer/. EpiAssembler/ VaccineCAD In Vitro HLA binding assay ELISpot - ELISA - Multiplex ELISA - FACS - T regulatory T cell profiling In Vector DNA prime/peptide (pseudoprotein boost) vaccines Vaccine delivery / formulation optimization / detolerizing delivery agents In Vivo HLA DR3, DR4 transgenic mice HLA class I transgenic mice Vaccination, Comparative studies
59. Prime-boost Smallpox Vaccine Immunization Sacrifice Birth 1. epitope DNA vaccine prime 2. epitope peptide boost 1. control DNA prime 2. control peptide boost Week 0 Week 8-14 IFN-gamma and multiplex ELISA Challenge Lethal Intratranasal Challenge 3 mice week 16 Week 18
60. Results: 100% survival of Vaccinated mice vs. 17% of placebo 100% 100% 0 20 40 60 80 100
61. No significant weight loss in vaccinated mice – surviving mice in placebo arm are regaining weight
62. HIV Vaccine Development The GAIA HIV Vaccine • In Development since 1998 - More than 300 epitopes mapped • Highly Variable Pathogen – Conserved epitopes • HLA Diversity -- 6 HLA supertypes • T cell help -- Immunogenic consensus sequence epitopes • Validation in HLA transgenic mice -- Good progress.