Tomorrow's vaccines today

Dr Odile Leroy Dublin, ESOF, 14th July 2012

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Opisthotonos    Sir  Charles  Bell,  1809.  

Neonatal  Tetanus  ,  CDC.  

1927: TetanusVaccine (Ramon and Descombey)

1980’s: ~ 1M Neonatal Tetanus death/year

2008: 54 000 NT deaths 92% reduction

My background

ESOF  2012  

Global  Immuniza4on  Mee4ng    18th  February  2009  

Yes,  We  Can!  

Maternal and Neonatal Tetanus Elimination

by 2012

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   China  :  10th  century    China    

1.  Scabs  from  mildly  affected  smallpox  pa4ents  

2.   Ground  up  (4:1)  with  Uvularia  grandiflora    3.  stored  1  month,  and    4.  inoculated  intranasally  

•   6  days  aRer:  fever  •   9-­‐10  days  aRer  rash    

«  not  one  in  10,  not  one  in  100  does  not  recover  »      

3 “I” paradigm

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Ø  Vaccines are powerful public health tool

200 years after Jenner : WHO declares the eradication of small pox

1965   1970   1975   1980  

Number of Countries with more than

one case per month

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(2011) malERA - a research agenda for malaria eradication. PLoS Collections 7(13): ev07.i13.

Malaria Eradication

(1960)  

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Long history of parasitism

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Vaccine development challenges

•  Heuristic, empirical approach •  All easy vaccines have been developed •  “Isolate-Inactivate-Inject” paradigm is

ineffective for hyper-variable pathogens – Malaria, shistosomiasis, HIV, RSV, chlamydia,

herpes…..

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Vaccine development challenges

•  Limits of empirical approach: –  Infection not controlled by neutralizing antibodies –  Immunity from disease prevent pathology but not spread –  Immaturity of immune system at time of exposure (RSV) –  Maternal Antibody transfer interferes with vaccine response

(RSV, measles) –  Genetic variability of pathogen / antigens –  Natural disease does not provide immunity (HIV, herpes..) –  Natural Immunity results from repeated infection (malaria) –  ……

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Vaccine development challenges

•  Inter-individual variation – Dosing – Immunogenicity – Safety

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Vaccinomics

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Nohynek H, Jokinen J, Partinen M, Vaarala O, Kirjavainen T, Sundman J, Himanen SL, Hublin C, Julkunen I, Olsén P, Saarenpää-Heikkilä O, Kilpi T. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood

narcolepsy in Finland. PLoS One. 2012;7(3):e33536.

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Age  distribu5on  of  the  new  narcolep5c  cases  among  the  Pandemrix  vaccinated  and  unvaccinated  children  and  adolescents.  

vaccinated  

non  vaccinated  

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5 10  

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HLA-­‐DQB1*0602  genotype.  

Personnalised vaccinology

ESOF  2012  

How to address those challenges in Europe?

The role of TRANSVAC European Network of Vaccine Research &

Development

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European vaccine R&D (still) strong

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The Public Vaccine Institutions in Europe

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Up to 90s Now Private

Still Public

NFIA  Holland nfiaholland@‏     Serum  Ins4tute  of  �#India�  �#SII�  buys  produc4on  facili4es  of  state-­‐owned  �#Netherlands�  Vaccine  Ins4tute  �#NVI�  h]p://bit.ly/LUtETe    �#nfia_news  10:58  PM  -­‐  2  Juill,  12  via  web  ESOF  2012  

What is needed?

•  To foster European Efforts for a global impact

•  To maintain and strengthen European Infrastructure : European leadership in vaccine R&D as driver force

www.transvac.org

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TRANSVAC Partners

Grenoble,  FR  

Ins4tuto  de  Biologia    Experimental  e  Tecnológica,  PT  

ESOF  2012  

A clear example of Integrating Activity

Service-oriented programme •  To provide trans-national access to researchers or

research teams : Delivery of services

– Adjuvant : vaccine formulation

– Vaccine pre-clinical animal model – Global analyses (ILLUMINA Deep Sequencing, AGILENT

Microarrays, AFFYMETRIX Microarrays)

– Stable assay and reference reagent standards platform

– GMP cell line bank for viral vector vaccine production

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•  To improve the services provided by the infrastructures (in quality and/or quantity)

•  Roadmap for improved services – developing trans-diseases research programmes

•  Immuno-assays for pre-clinical assessment or quality control assessment, or

•  Analysis or physical-chemical characteristics of antigen/adjuvant formulations, in a regulatory perspective,

•  Proteomic/transcriptomic analysis of clinical trial samples

A clear example of Integrating Activity

Service-oriented programme

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A clear example of Integrating Activity

Service-oriented programme •  To foster a culture of cooperation between

the research infrastructures and the related scientific communities – Interlab interactions to qualify / validate

reference reagents

– Harmonisation of immunoassay systems; clinical trials analysis

– Laboratory communication, data sharing, modular course on vaccine development

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Meredith  Wadman  NATURE.439  2006  

The Goal – The end of them and us

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Acknowledgements EVI donors DGIS Irish Aid German BMBF EC FP6/FP7

Scientific Community Europe Africa India

EVI EEIG members –  Stockholm University, SE –  Heidelberg University , DE –  Royal College of Surgeon in Ireland, IE –  Jenner Vaccine Foundation-University of

Oxford, UK –  Biomedical Primate Research Centre NL –  National Institute for Public Health and the

Environment, NL

Volunteers in EVI funded clinical trials

EVI sub-contractors, CMOs, CROs, Consultants

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