Vaccini come paradigma di ricerca al servizio della salute globale

8/13/2019 Vaccini come paradigma di ricerca al servizio della salute globale

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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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'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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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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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

Vaccini come paradigma di ricerca al servizio della salute globale

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