institute for immunology and informatics (icubed) d. spero icubed overview 2011 uri biotechnology...

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

GAIA Vaccine Foundation Project West Africa (Bamako, Mali)

http://www.GAIAVaccine.org

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

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

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

The Goal- Prevent Disease

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.

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?

“Old Style” Vaccines

Shake . . . and bake – That was then

How the Flu Vaccine is made

Sanofi Pasteur

50 year old technology, growing influenza virus inchicken embryos- doesn’t work with avian flu.

• Molecular biology• High throughput sequencing• Genomics / proteomics• Bioinformatics• Computational power

Accelerating Drivers

Accelerating Vaccine DesignFrom Genome to Vaccine

Vaccine Design Tools and Techniqueshttp://www.epivax.com/platform

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iVAXToolkit

Strain 1

Strain 3

Strain 2

core genomedispensable genes

strain-specific genespangenome

Comparative Genomics ImpactsVaccine Immunogen SelectionComparative Genomics

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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August 25, 2011

Epitopes Conserved over Time & Space

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

DNA – chain of epitopes, or peptide in liposomes ICS-optimized proteins in VLPICS-optimized whole proteins

Vaccine FormulationsOther Formulations

IVAX Toolkit: In use by Researchers funded by the NIHCooperative Centers for Human Immunology CCHI

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iVAX Toolkit On Line Access

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

Neglected Tropical Diseases

Leading Causes of Life-Years Lost to Disability and Premature Death

DISEASELower Respiratory Infections

HIV/AIDS

Unipolar Depression

Diarrheal Disease

Ischemic Heart Disease

Neglected Tropical Diseases

Cerebrovascular Diseases

Malaria

Road Traffic Accidents

Tuberculosis

DALYs

91.4 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

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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Immunogenic

Epitopes

Shared

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Epitopes

smallpoxvaccinia

Immunome-Derived Monkeypox Vaccine:VennVax

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

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Survival of VennVax-Vaccinated Mice After Aerosol Challenge

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Moise et al. Vaccine. 2011; 29:501-11

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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HelicoVax Eradicates H. pylori Infection

This result accomplished in just over 24 months . . .

Moss et al, Vaccine 2011;29:2085-91

Next Step in Vaccine Evolution?

PigMatrix FishMatrix

And . . . .

“That was then”: How the Flu Vaccine is made

Sanofi Pasteur

50 year old technology, growing influenza virus inchicken embryos

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

Pathogen Genome(s)

Genome-DerivedVaccine Components

Faster! The “Gene to Vaccine” – 60 days

Funding from DARPA for this approach to be announced this week!

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.

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

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

Providing students with the right skill set

• Immunology• Vaccinology• Protein Manufacturing• Entrepreneurship• Neglected Tropical

Disease Training• Vaccine Renaissance

Conference

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

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

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

The iCubed Team