Vaccination: Canada’s leadershipover the last century

Lorne A Babiuk

University of Alberta

May 26 - 2015

Outline• Introduction

• Process for vaccine development

- engagement of multiple partners

• Landscape

- VIDO, CAIRE,CCV

• Opportunities

• Challenges

Why infectious diseases?• Approximately 1/3 of all annual deaths are

directly due to infectious diseases

• Some cancers caused by infectious diseases

- liver cancers -- HCV, Hep B

- cervical cancer -- HPV

• 30 new emerging or remerging diseases occurred over last 30 years- many are zoonotic

• Animal diseases threaten global food security

Global challenges• Currently 1 billion people go to bed hungry

• By 2050 2 billion more people

• Decreased land resources/climate change

• Livestock a reliable source of income/protein

• Increase production of milk ,meat and fish

• 500 million smallholders support 2 billion

• Almost 2/3 of poor livestock keepers are women

• Healthy animals=healthy food=healthy people=

Increased economic stability

Economic impact of animaldiseases

• BSE- UK $ 1 billion direct compensation

• BSE – Canada $ 8 billion total losses

• BRD - $ 1 billion annually

• Scours $ 500 million annually

• FMD 2001 $ 6 billion

• Emerging diseases unknown

- SARS $ 100 billion

Infectious Diseases Spread Easily

• Canadians remain at risk

Canada has played a pivotal role in global vaccine development

• Paralytic Polio: Connaught laboratory– Medium 199 & Toronto Method

– Large scale production of polio vaccine

• 1st combined vaccine (DPT)

• 1st infant Meningitis C vaccine (NRC)

• World first genetically engineered animal vaccine ( VIDO)

• 1st zoonotic vaccine (VIDO-InterVac)

• Protein misfolding vaccine development

• Ebola (NML)

Collaborations in Infectious Diseases

Infectious

Diseases

Information

Technology

Commercial

companies

Pathogenesis

Immunology

Health care

delivery

Diagnostics

Therapeutics/

prophylactics

Epidemiology

Public Health

Clinical

Collaborations in Infectious Diseases

Therapeutics/

Prophylactics

Clinical trials Toxicology

Infrastructure

human/physical

Manufacturing

Microbiology/

immunology

RegulatoryFormulation IP

Genomics/

proteomics

Delivery

Bioinformatics

Ethical/cultural

Partners in vaccine development

PATH FOR VACCINE LICENSURE

Antigen

Identification

Host

Responses

Delivery

Safety

Immunogenicity

Efficacy

Immunogenicity

Dose

Efficacy

SafetySafety

Phase I

10-100

Phase II

100-1000

Phase III

1000+

Phase IV

$1 million $5 million $$ $$ $$$

$$$$

2 years 8-10 years

Preclinical Clinical

Funding

• Basic research - Federal /provincial agencies

• Translational research ( early ) -governments/angel investors

• Commercialization – venture capital/ company

• Marketing - company

Preclinical $

Antigen

IdentificationAntigen

ProductionFormulation

Proof-of-

Principle

(models)

GMP

Production

• Genomics

• Comparative biology

• Immunology

• Brute force

1. Antigen Identification

Preclinical $

Antigen

IdentificationAntigen

ProductionFormulation

Proof-of-

Principle

(models)

GMP

Production

2. Antigen Production

• Prokaryotic – cost

• Eukaryotic– CHO

– yeast

– plants

Preclinical $

Antigen

IdentificationAntigen

ProductionFormulation

Proof-of-

Principle

(models)

GMP

Production

- Alum - Th2

- MF59

Multiple adjuvants

Toll receptors– CpG

– Polyphosphazene

– HDP

3. Formulation

Preclinical $

Antigen

IdentificationAntigen

ProductionFormulation

Proof-of-

Principle

(models)

GMP

Production

4. Proof-of-Principle (models)

• Mice ( often lie)– Non-human primates

– Two animal rule

Are Animals perfectModels of human disease?

Preclinical $$

Antigen

IdentificationAntigen

ProductionFormulation

Proof-of-

Principle

(models)

GMP

Production

5. GMP Production

• Calibrate all equipment– Reconfirm all components

– Audit pathway

Clinical $$$$

Phase I

SafetyPhase II

Safety

Phase III

SafetyLicensure Marketing

1. Phase I Safety

• 10-20 individuals safety

Clinical $$$$

Phase I

SafetyPhase II

Safety

Phase III

SafetyLicensure Marketing

• Safety and efficacy - 20-100 individuals

2. Phase II Safety

Clinical $$$$

Phase I

SafetyPhase II

Safety

Phase III

SafetyLicensure Marketing

3. Phase III Safety

• 100+ individuals

• Efficacy and safety

• Combination with other

vaccines- microbiome

Clinical $$$$

Phase I

SafetyPhase II

Safety

Phase III

SafetyLicensure Marketing

4. Licensure

• FDA approval

Clinical $$$$

Phase I

SafetyPhase II

Safety

Phase III

SafetyLicensure Marketing

• Post-marketing surveillance

5. Marketing

Funding opportunities along thecontinuum

• Basic Research

- Federal /provincial granting agencies

• Translational research

- Federal/provincial agencies/industry

• Commercialization

- Industry/ angel investors

• Marketing

- Industry

Federal /Provincial agencies

• Tri-council

- NSERC- discovery , strategic ,CRD, industrial chairs. CIHR- operating , foundational, RxD , SSHRC, NCE’s

• NRC

- IRAP

• Regional Development Agencies

National Centers of Excellence

• Canadian bacterial disease network

• CANVAC

• PrioNet

• GlycoNet

• BioCanRx

• PREVENT

Canadian Landscape Examples

The Vaccine and Infectious Disease Organization –

International Vaccine Centre

Design Update: Main Floor Plan

Clinical

Pathology

CL3 Laboratories

Necropsy/Restricted Lab

Officially ‘hot’

VIDO-InterVac

• 165 personnel

• ISO9001 Certified

• Expertise in large animal models of disease

• 8 commercialized vaccines; 6 world firsts

• >$200 million in state-of-the-art infrastructure

• CL2 (VIDO)

– ~100,000 ft2 of labs + 20,000 ft2 animal isolation

– 160 acre research station

• CL3 (InterVac)

– 150,000 ft2 (~13 hockey rinks)

– 18 animal holding rooms; 6 laboratories

– Select agent lab

– Aerobiology challenge capability (e.g., Flu, TB)

• A not-for-profit corporation - funding from NCE CECR

• Goal to help with translation/accelerate vaccines to the marketplace

• 3 nodes: BC, SK, NS

• Currently 5 vaccine candidates in the pipeline

Canadian Association for

Immunization Research and

Evaluation

(CAIRE)

A UNIQUELY CANADIAN INNOVATION

CAIRE Members

>140 Canadian researchers and stakeholders from more

than 30 institutions across Canada, representing a majority

of those involved in translational research

Members include leading specialists in infectious diseases,

public health, microbiology, clinical trials, vaccine

immunology and technology assessment, social and

behavioral science, nursing research, epidemiology,

biostatistics and modeling.

Mission

To encourage and enhance vaccinology research so that

Canadians have timely access to new and improved

vaccines and optimal programs.

By:

Creating a positive climate for vaccine research

Expanding collaboration and networking

Encouraging excellence in research

Supporting and encouraging young investigators

Implementing novel education initiatives

CAIRE INNOVATIONS

Working with industry to improve the culture of

vaccine trials; attract more trials to Canada

Attending the National Advisory Committee on

Immunization to be alert to research needs

Provided framework for National Vaccine Research

networks, including Pandemic Flu trials

Master Classes and other learning venues to keep

members and stakeholders current

CAIRE Research Sponsors Advisory Board

Innovative, neutral forum for the advancement of

applied vaccinology research in Canada

Participants include academic investigators, public

health leaders and representatives of 5 major vaccine

companies

Board meets 2x yearly to discuss items of mutual

interest, including unique domestic strengths and

evolving opportunities that favor Canada as a trials

location with multinational companies

CAIRE Research Promotion

CAIRE’s promotion of Canadian research

strengths/opportunities has included:

Presentations about surveillance programs that

could inform product development

Opportunities to conduct research in special

populations

Opportunities to utilize major national networks

such as PCIRN, CIRN, IMPACT

Opportunites for research using administrative

databases, social science research etc

CAIRE Research Advocacy

Partnered with PHAC and CIHR to sponsor Research

Priority Workshops in 2005 on Influenza and HPV

In 2012 CAIRE brought Canadian vaccinology

stakeholders (industry, public health, academia)

together to discuss how to enhance partnerships in

vaccine-based disease prevention

2013 Workshop on improving access to recommended

but non-funded vaccines

CAIRE Research Education

Some of CAIRE’s research education initiatives have

included:

Co-developing the Canadian Immunization

Conference to ensure ample vaccine science

Master Classes on Intelligent vaccine and program

design

Round Table on Meningococcal disease prevention to

identify research priorities

Canadian Center forVaccinology

An integrated interdisciplinary approach

to vaccine discovery, evaluation, and

health policy and translation

Shelly McNeil, Joanne Langley, Scott Halperin

Scott Halperin, Director

Vision

To develop, implement and evaluate vaccines for infectious

diseases that have a significant impact on Canadian and global

health, and to train experts in these critical fields. This is

achieved through strength in discovery science, evaluation

research, and health policy and translation through the applied

study of the social sciences and humanities (ethics, law, and

society).

• 7,000 sq feet – virology, bacteriology, molecular biology and immunology basic research including Level 3 lab

• 2,500 sq ft – health policy and translation research

• 5,500 sq ft – ambulatory clinical trial space

• 5,000 sq ft – inpatient Vaccine Challenge/Clinical Research Unit

Facilities and Progressto Date

Laboratories

Level 3

Clinical Trials Research Center

Vaccine Challenge / Clinical Research Unit

Challenges• Funding

• Production of cGMP materials ?

• Anti-vaccine lobby

Acknowledgements• CAIRE

• CCfV

• VIDO/Intervac