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Vaccini come paradigma di ricercaal servizio della salute globale
Rino Rappuoli
Scienza e industriaRicerca e innovazione in biomedicina
Universit Bocconi ,Milano, 27 novembre 2013
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people live longer
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3
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4
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The unfinished cathedral
In Siena, anunfinished cathedralis the largest existingmonument toInfectious iseases,standing reminder ofa flourishing econom!
and culture wipedout forever in justthree months by the1348 PL !"#
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Smallpox: An Ancient and Deadly Disease
Daniel Bernoulli(mathematician and physician;1700 1782) estimated that, in
Europe, there were, onaverage, ca. 600,000 deaths
each year from Smallpox.
European population ca. 80M
E ery year 1 person e ery 1!0 died"rom the disease
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Smallpox: An Ancient and Deadly Disease
#1707 $%& o" 'sland population died
#1709 1!,000 died in (aris
#1753 20,000 died in (aris
#1768 %0,000 died in )aples
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"#$ %lobal &ction 'lanhttp())***+*ho+int)immuni ation)global-vaccine-action-plan)%.&'-doc-2011-2020)en)index+html/
0
So far saved >700 million disease cases,>1 0 million deat!s
"011#"0"0 vaccines $ill save
" million deat!s
2+ million)!ear 7000)da!
300)hour )min
Vaccination, t!e most effective medicalintervention ever introduced
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rom enner to 'asteur to #illeman
%solate %nactivate
%n&ectthemicroorganism causing disease
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uring the last 30 !ears, several ne* technologies madepossible vaccines that *ere previousl! impossible
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uring the last 30 !ears, several ne* technologies madepossible vaccines that *ere previousl! impossible
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'eningococcal disease
Tragediescovered by media
Severedisability
Death
(aused b) Neisseria meningitidis capsular serogroups *, B, (, +, 1-
reaming the ol!mpic gamesli e 'istorius
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uring the last 30 !ears, several ne* technologies madepossible vaccines that *ere previousl! impossible
5on6ugate vaccines
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#aemophilus influen ae t!pe 8#ib/
'neumococcus
Meningococcus
%roup streptococcus
(apsular pol)sacc!arides . (on&ugates
5apsule
5apsule
'ol!saccharide
5on6ugate
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(on&ugate vaccines for 'eningococcus (eliminated t!e disease in t!e U/
9aborator! 5onfirmed 5ases of :erogroup 5 Meningococcal isease8;ngland < "ales/
ee o2 8totals from mid=!ear/
.accine:ince the introduction of the >? Men5 vaccine in 1@@@>1-,000 cases prevented
A 1,300 deaths preventedA2,7 0 permanent seBuelae prevented
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Meningococcus capsule is a self antigenand cannot be used for vaccination
i h l 30 ! l * h l i d
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uring the last 30 !ears, several ne* technologies madepossible vaccines that *ere previousl! impossible
Reverse Vaccinolog)
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Ceverse vaccinolog!a genomic approach to vaccine discovery
In silico vaccinecandidates
;xpressrecombinant
proteins
VACCINE CANDIDATES
D00 potential vaccine candidatesidentified
3 0 proteins successfull! expressedin ;+coli
@1 novel surface=exposedproteins identified
2 novel proteinshave bactericidal
activit!
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3('enB Vaccine (omposition
Three protein antigens 8t*o fusion proteins and one single pol!peptide/
$uter Membrane .esicle 8$M./ component 8EF 'or& is '1+4/
Dose NHBA-GNA1030fHbp-
GNA2091 NadA OMV Al3+
0.5ml 50 g 50 g 50 g 25 g 0.5 mg
45Men is a suspension for in6ection
(lass
4or*
(lass 3
4orB
54S
6'V
f# ' Ead& E# &
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(linical evelopment
%nfants and c!ildren "mont!s to 8" )ears of age
G 9 0 received at least 1 dose of;H:;C$
G32 received booster dose in second!ear of life
*dolescents and adults :11 )ears ofage
G 170- *ere included
(!ildren " to 10 )ears ofage
G" 0 *ere included
I;valuated in 13 studies including @ randomi,ed controlled clinical trials+
Immunogenicity, Persitance, Concomitant administration, Tolerability
9 0
170-
" 0
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'enB Vaccine U/ media
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enB Vaccine U/ media 5#M' positive opinion 1D Eovember 2012
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To*ards a meningitis free *orld
The first vaccine lot *as released this *eeEo* *e can eliminate meningococcal meningitis
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Ceverse vaccinolog! allo*ed us to target man!pathogens that *ere difficult or impossible before
Including SUPER U!S
" n t i b i o t i c r e s
i s t a n t # # # #
S t a p h y l o c
o c c u s E$ c o
l i
C$ d i % % i c i l e
P s e u d o
m o n a s
S U P E R U ! S # #
#
;roup B Streptococcus
;roup * Streptococcus (!lam)dia 'alaria
+ersinia pestis
45Men first genome derivedvaccine
uring the last 30 !ears, several ne* technologies made
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uring the last 30 !ears, several ne technologies madepossible vaccines that *ere previousl! impossible
&d6uvants
M @( oil=in=*ater ad6uvant licensed *ith seasonal trivalent 81@@7/ and
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M @( oil=in= ater ad6uvant licensed ith seasonal trivalent 81@@7/ andpandemic monovalent vaccineProgenitor of other oil-in-water based adjuvants
'< = ad&uvant emulsion
oil
S4* 9 ?? 90*ntigens
1D0nm6il#in#$ater emulsion ad&uvantlicensed for use in seasonalinfluenza vaccine
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g gpossible vaccines that *ere previousl! impossible
:!nthetic seeds
:elf &mplif!ingMessenger CE&8S*'C
S)nt!etic biolog)
%nfluenza, eggs . cell culture
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, ggtime to retire the eggsL
TechnoIog! of 1@30 s
5ell culture, licensed b! the & in 2012
& s!nthetic Influen a accine :eed in da!s
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& s!nthetic Influen a .accine :eed in da!sshipping information instead of viruses
uring the last 30 !ears, several ne* technologies made
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possible vaccines that *ere previousl! impossible
"hat do *e do *ith allthese technologiesL
f
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.accines have been developed for childrenWith an aging society, we need a new model for health care
R.Rappuoli, C. andl, !" #lac$ , %. &e 'regorio (ature Reviews Immunology N Eovember 2011O doi(10+103 )nri30
Vaccines for ever) age
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Vaccines for ever) age
R.Rappuoli, C. andl, !" #lac$ , %. &e 'regorio (ature Reviews Immunology N Eovember 2011O doi(10+103 )nri30
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accines against povert!
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.accines against povert! &n Institute to address the gaps in vaccine development
In the recent past, no mechanism as in place to developvaccines needed only in developing countries
1ovartis Vaccines %nstitute for ;lobal Bealt! A1V;BC
& ne* non#profit initiativeto develop effective and affordable vaccines for neglected infectious diseases of developing countries
9ocated in :iena , Ital!9egal entit! started in eb 2007
&llan :aul hired as 5;$ :ept 2007Inauguration
eb 22, 200)p!oid vaccine licensed to Bio?
post p!ase %%, Fune "01-
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Master Program in Vaccinology &Pharmaceutical Clinical Development :
G)as reached so far *+ countries of thedeveloping world
G70J of the former students are activel!*or ing in the vaccinolog! field
G ormer students are follo*ed for !
Fobs investments brains
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Fobs, investments, brains
1==" "00E "01-
Fobs 234 1100 2000
%nvestments ======2 0M=====%nvestments in R. ===== @0M=====
4eople 4 J of our collaborators are *omen
4 J are graduated emplo!ees40J are less than 3 !ears old
5ollaborators come from 43 different countries
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