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Vaccines of the future Rino Rappuoli Conference on New Horizons for Vaccine Research and Innovation Session on Innovation on Vaccine Design Bruxelles, March 12 2014
Transcript of Vaccines of the future - European Commission · Vaccines of the future Rino Rappuoli Conference on...
Vaccines of the future
Rino Rappuoli
Conference on New Horizons for Vaccine Research and Innovation Session on Innovation on Vaccine Design
Bruxelles,
March 12 2014
Vaccination, the most effective medical intervention ever introduced
• So far saved >700 million disease cases,
– >150 million deaths
• 2011-2020 vaccines will save
– 25 million deaths • 2.5 million/year
• 7000/day
• 300/hour
• 5/min
From Jenner to Pasteur to Hilleman
Isolate
Inactivate
Inject the microorganism causing disease
During the last 30 years, several new technologies made
possible vaccines that were previously impossible
Today we see an explosion of new technologies
2014
Conjugate vaccines
Haemophilus influenzae type B (Hib)
Pneumococcus
Meningococcus
Group B streptococcus
Capsular polysaccharides & Conjugates
Capsule
Capsule
Polysaccharide
Conjugate
Reverse Vaccinology
In silico vaccine candidates
Express recombinant proteins
VACCINE CANDIDATES
600 potential vaccine candidates identified
350 proteins successfully expressed in E.coli
91 novel surface-exposed proteins identified
28 novel proteins have bactericidal
activity
Reverse Vaccinology A genomic approach to vaccine discovery
Bexsero in Princeton
Reverse vaccinology allowed us to target many pathogens that were difficult or impossible before
Including SUPERBUGS
Group B Streptococcus
Group A Streptococcus
Chlamydia
Malaria Yersinia pestis
MenB first genome derived
vaccine
Adjuvants
Fluad
TIV
–
0.6
–
0.4
–
0.2
0.0
0.2
0.4
0.6
0.8
1.0
Va
cc
ine
eff
ica
cy
vs
. n
on
-in
flu
en
za c
on
tro
l
0 20 40 60 80 100 120 140 160 180 200 220
Days post-second dose
Vesikari T, et al. NEJM.
MF59 increases efficacy of influenza vaccine in
children from 43 to 86%
Vaccine also showed satisfactory
safety profile:
• Increased local reactogenicity
• No increase in serious adverse
experiences vs. control
Comparative immunogenIcity testing of
ADITEC adjuvants:
CAF01
IFN-y IL-5 IL-17 IL-20
1000
2000
3000
4000
pg
/ml
CAF01
IFN-y IL-5 IL-17 IL-20
500
1000
1500
2000
2500
CAF01
IFN-y IL-5 IL-17 IL-20
5000
10000
15000
pg
/ml
IC31
IFN-y IL-5 IL-17 IL-20
1000
2000
3000
4000
pg
/ml
IC31
IFN-y IL-5 IL-17 IL-20
2000
4000
6000
8000
IC31
IFN-y IL-5 IL-17 IL-20
500
1000
1500
2000
pg
/ml
MF59
IFN-y IL-5 IL-17 IL-20
500
1000
1500
pg
/ml
MF59
IFN-y IL-5 IL-17 IL-20
500
1000
1500 MF59
IFN-y IL-5 IL-17 IL-20
200
400
600
800p
g/m
l
GLA-SE
IFN-y IL-5 IL-17 IL-20
500
1000
1500
pg
/ml
GLA-SE
IFN-y IL-5 IL-17 IL-20
500
1000
1500
GLA-SE
IFN-y IL-5 IL-17 IL-20
500
1000
1500
pg
/ml
H56
Tuberculosis
MOMP
Chlamydia Hemagglutinin
Influenza
CAF01
6h
24h
72h
30%
70%
25%
75%
70%
30%
95%
5%
54%
46%
Transcriptomics analysis of ADITEC adjuvants
Structural
Vaccinology
Structure-based
antigen design
Pre-fusion
Post-fusion
Structural Vaccinology the RSV example
• Synthetic seeds
• Self Amplifying Messenger RNA (SAM)
Synthetic biology
A synthetic Influenza Vaccine Seed in 5 days shipping information instead of viruses
Systems biology
Systems biology From 10,000 people with 10 data each
to
10 people with 10,000 data each
ADITEC: 13 Clinical Studies
Can these
technologies help
the aging society?
Vaccines for every age
R.Rappuoli, C. Mandl, S: Black , E. De Gregorio
Nature Reviews Immunology | November 2011; doi:10.1038/nri3085
Vaccines for today’s society
Vaccines against poverty An Institute to address the gaps in vaccine development
In the recent past, no mechanism was in place to develop vaccines needed only in developing countries
Novartis Vaccines Institute for Global Health (NVGH)
A new non-profit initiative to develop effective and affordable vaccines for
neglected infectious diseases of developing countries
Located in Siena , Italy
Legal entity started in Feb 2007
Allan Saul hired as CEO Sept 2007
Inauguration Feb 22, 2008
Typhoid vaccine licensed to BioE post phase II, June 2013
Which organization
for vaccine
development?
Maurice Hillemann One man, nine vaccines, that practically every child gets
Collaboration of many partners is necessary for a vaccine development
(Big science)
challenges for vaccine
development
• Fatigue Immunization typically prevents diseases, which have been nearly eradicated, so most people lack first-hand experience
• Vaccine value in a world of limited resources cost effectiveness becomes important in decision making Health economics not able to assign the right value to vaccines
• Saving money or saving lives? – Should industry invest in vaccines?
2012
2013
Fatigue, misperceptions, failure to assign the right value to vaccines
SMART
VACCINES
Strategic Multi-Attribute Ranking- Toll (SMART) Vaccines
28 attributes 8 categories
Institute of Medicine (IOM) initiative SMART Vaccines
From Cost/QALY
To Cost/QALY +
27 attributes
