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Institute for Immunology and Informatics (iCubed)
D. Spero icubed overview 2011
URI Biotechnology Program in ProvidenceThe College of the Environment and Life
SciencesUniversity of Rhode Island
www.immunome.orgURI Alumni Board 2012
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GAIA Vaccine Foundation Project West Africa (Bamako, Mali)
http://www.GAIAVaccine.org
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Institute for Immunology and Informatics (iCubed)
Our Mission: To design safer, efficacious vaccines and therapeutics to
prevent and cure human and animal disease using novel computer-based (informatics) immunology tools
Focus: Accelerated vaccine discovery for infectious diseases and
biodefense
D. Spero URI Alumni Board 2012
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The iCubed Leadership
Annie De Groot, M.D.• Research Professor and Director iCubed
• CEO EpiVax Inc.
Expertise: Immunology, Immunoinformatics,
Vaccine Research, Infectious Diseases,
Autoimmunity, Biotechnology
Denice Spero, Ph.D.• Research Professor and Co-director iCubed
• Former President of Developing World Cures, Inc.
• Vice President Drug Discovery Boehringer Ingelheim Pharmaceuticals, Inc.
Pharmaceutical Leader, Experienced Drug Developer
Expertise: Drug metabolism and pharmacokinetics, Drug Safety, Drug Formulation, Organic
Chemistry, Autoimmune Diseases, Developing world diseases, Pharmaceutical industry
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Why Are Vaccines so Important?
Vaccines are the single most cost effective means of controlling the spread of infectious disease
No public health tool has improved global health more than vaccines
D. Spero URI Alumni Board 2012
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The Goal- Prevent Disease
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Why are Vaccines a Hot Commodity ?
After years of beating a retreat from making vaccines, the world's biggest drug companies are piling back in. Vaccines are giving the drug business a shot in the arm. . . .For example, Johnson & Johnson paid $441 million for a stake in Crucell, a Dutch vaccine firm, and . . .
. . . just last week, Roche snatched up Illumina for $5.7B.
Through the deal, Roche would pick up technology to read the genetic makeup of tumors, boosting the potential for targeted personalized medicine in this area, as Bloomberg notes.
What are some of those medicines? Well, of course, Vaccines.
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Better understanding of vaccine MOA
Improve vaccine safety and efficacy
The Focus: Better, Faster Vaccines
Accelerate Vaccine Design
The Evolution of Vaccines
Vaccines are evolving rapidlyCan we make them even Faster – Safer – Better?
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“Old Style” Vaccines
Shake . . . and bake – That was then
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How the Flu Vaccine is made
Sanofi Pasteur
50 year old technology, growing influenza virus inchicken embryos- doesn’t work with avian flu.
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• Molecular biology• High throughput sequencing• Genomics / proteomics• Bioinformatics• Computational power
Accelerating Drivers
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Accelerating Vaccine DesignFrom Genome to Vaccine
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Vaccine Design Tools and Techniqueshttp://www.epivax.com/platform
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iVAXToolkit
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Strain 1
Strain 3
Strain 2
core genomedispensable genes
strain-specific genespangenome
Comparative Genomics ImpactsVaccine Immunogen SelectionComparative Genomics
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Protective epitopes
Potentially detrimental cross-reactive epitopes
Potentiallydetrimental cross-reactive epitopes
Safer: remove conserved epitopes
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Conservatrix: Overcome the Challenge of Variability
HIV HCV Influenza
Conserved Epitope-allows protection vs. more strains w/ fewer epitopes.
CTRPNNTRK
CTRPNNTRKCTRPNNTRK
CTRPNNTRKCTRPNNTRK
CTRPNNTRK
CTRPNNTRK
Overcome Strain Variation- Conservatrix
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Confidential17
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GAG Epitopes
GAG-3003
GAG Sequences
GAG-1012
GAG-1014
GAG Random
GAG-1261
GAG-1013
August 25, 2011
Epitopes Conserved over Time & Space
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DNA Vector
DNA insert
Intended Protein Product: Many epitopes strung together in a “String-of-Beads”
Reverse Translation: Determines the DNA sequence necessary to code for the intended protein. This DNA is assembled for insertion into an expression vector.
Protein product (folded)
Making the Vaccine
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DNA – chain of epitopes, or peptide in liposomes ICS-optimized proteins in VLPICS-optimized whole proteins
Vaccine FormulationsOther Formulations
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IVAX Toolkit: In use by Researchers funded by the NIHCooperative Centers for Human Immunology CCHI
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iVAX Toolkit On Line Access
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iVAX – for Neglected Tropical Diseases
• Protozoan Infections– African
Trypanosomiasis– Chagas Disease– Leishmaniasis
• Bacterial & Viral Infections– Buruli Ulcer– Dengue– Leprosy– Trachoma**
• Helminth (Worm) Infections– Soil-Transmitted
Helminth Infections• Ascariasis**• Hookworm**• Trichuriasis**
– Schistsosomiasis** – Lymphatic Filariasis**– Onchocerciasis**– Dracunculiasis
**indicates one of “The Big Seven” NTDs
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Neglected Tropical Diseases
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Leading Causes of Life-Years Lost to Disability and Premature Death
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DISEASELower Respiratory Infections
HIV/AIDS
Unipolar Depression
Diarrheal Disease
Ischemic Heart Disease
Neglected Tropical Diseases
Cerebrovascular Diseases
Malaria
Road Traffic Accidents
Tuberculosis
DALYs91.4 million
84.5 million
67.3 million
62.0 million
58.6 million
56.6 million
49.2 million
46.5 million
34.7 million
38.7 million
Funding Per DALY
$0.62
Global Burden of Infectious Disease
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Burk/Tuly/MP
Current Vaccine Design Pipeline
Epitope Discovery
Epitope Validation
Construct Design
Immuno-genicity
HIV/TB Epitope Discovery
Epitope Validation
Construct Design
Immuno-genicity
Tularemia Epitope Discovery
Epitope Validation
Construct Design
Immuno-genicity Animal Model Validation
Monkeypox Epitope Discovery
Epitope Validation
Construct Design
Animal Model Validation
H. pylori Epitope Discovery
Epitope Validation
Construct Design
Animal Model Validation
VEE/Wee Epitope Discovery
Epitope Validation
Construct Design
Animal Model Validation
Animal Model Validation
Animal Model Validation
Immuno-genicity
Immuno-genicity
Immuno-genicity
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Vaccine
Immunogenic
Epitopes
Shared
Immunogenic
Epitopes
smallpoxvaccinia
Immunome-Derived Monkeypox Vaccine:VennVax
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Prime-Boost Immunization with VennVax
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Immunization Sacrifice 3 mice Week 16
1. epitope DNA vaccine prime2. epitope peptide boost
1. control DNA prime2. control peptide boost
Week 8-10
IFN
-g
mul
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x EL
ISA
Aerosol challenge
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Survival of VennVax-Vaccinated Mice After Aerosol Challenge
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100% survival of Vaccinated mice vs. 17% of placebo
Moise et al. Vaccine. 2011; 29:501-11
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Therapeutic H. pylori Vaccination
Week 0 Week 6 Week 12-19 Week 51
IFN-gamma and IL-4 ELISpot
Histology
1. epitope DNA vaccine prime IM2. epitope peptide boost IN
H. pylori SS1
H. pylori SS1
H. pylori SS1
H. pylori SS1 lysate IN
1. epitope DNA vaccine prime IN2. epitope peptide boost IN
1. control DNA prime IN2. control peptide boost IN
H. pylori SS1
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Lysate pVAX DNA IM DNA IN
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i qPC
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*** P<0.001
** P<0.01
*** P<0.001
HelicoVax Eradicates H. pylori Infection
This result accomplished in just over 24 months . . .
Moss et al, Vaccine 2011;29:2085-91
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Next Step in Vaccine Evolution?
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PigMatrix FishMatrix
And . . . .
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“That was then”: How the Flu Vaccine is made
Sanofi Pasteur
50 year old technology, growing influenza virus inchicken embryos
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This is Now!The iCubed “Gene to Vaccine” Approach
No whole viruses or bacteria: Fast and targeted!
Genome of the pathogen
Select pathogen proteins
String peptidestogether to make avaccine
Selectpeptides that will interact with the human immune system
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Pathogen Genome(s)
Genome-DerivedVaccine Components
Faster! The “Gene to Vaccine” – 60 days
Funding from DARPA for this approach to be announced this week!
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A bold statement:
Personalized vaccines will be a reality in 10 to 15 years.
How so? Because the technology that can design safe, effective vaccines already exists, right here at URI.
Moving vaccine development from 20 years to 20 minutes is the next step.
What is needed ? Vision. Leadership. Financial and Infrastructure Support.
“Yes we can!” We are able to make better, safer and faster vaccines, and also develop a workforce that is prepared to bring that dream to fruition.
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New Challenges/ New Opportunities
Emerging Infectious Disease Threats
Unprecedented infectious disease threats (population density, global travel, global warming, widespread bioengineering technology and capabilities)
Advances in genomics, microbiology and immunology create an opportunity to re-think current processes
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How are we meeting the challenge? iCubed Research Areas
Applying New Tools to Design New, Safer and Faster Vaccines:
Biodefense - defending our military and our communities Infectious diseases - Hepatitis C, H. pylori, emerging ID Cancer - New collaborations with cancer experts Tropical Diseases - Developing world and Southern US FarmVax - Fish, swine, chickens to protect our food,
protein sources
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Providing students with the right skill set
• Immunology• Vaccinology• Protein Manufacturing• Entrepreneurship• Neglected Tropical
Disease Training• Vaccine Renaissance
Conference
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The Business Side of iCubed
Vision: To Build URI as the Major Center for Next
Generation Vaccine Discovery in the World Entrepreneurial Model
Primarily self-funded through grants and overhead return
Seeking Private Funding to:
• Expand research projects
• Support faculty and laboratory space
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iCubed Trajectory
Opened 2008 – 3 full time staff, several part time
faculty
As of 2012 - 15 scientists and staff
Many Collaborations: Brown/Lifespan, Dartmouth,
UConn, NIH (LPD) USDA (ARS), DoD, Peru (Cayetano
Heredia), Thailand, Indonesia (Eijkman Institute)
Awarded grants since inception: $11.3 M dollars
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Institute for Immunology and InformaticsLifespan, URI, EpiVax 2009
Translational Research on Immunome-Derived Accelerated VaccinesProjects at the Institute for Immunology and InformaticsIn collaboration with EpiVax
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The iCubed Team