Vaccini come paradigma di ricerca al servizio della salute globale

Rino Rappuoli
Scienza e industria
Ricerca e innovazione in biomedicina Universit Bocconi, Milano, 27 novembre 2013

people live longer

The unfinished cathedral

In Siena, an unfinished cathedral is the largest existing monument to Infectious iseases, standing reminder of a flourishing econom!

and culture wiped out forever in just three months by the 1348 PL !"#

Smallpox: An Ancient and Deadly Disease

Daniel Bernoulli (mathematician and physician; 1700 1782) estimated that, in Europe, there were, on average, 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

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

Vaccination, t!e most effective medical intervention ever introduced

So far saved >700 million disease cases, >1 0 million deat!s

"011#"0"0 vaccines $ill save

" million deat!s

2+1 million)!ear 7000)da! 300)hour 1)min "#$ %lobal &ction 'lan
http())***+*ho+int)immuni,ation)global-vaccine-action-plan)%.&'-doc-2011-2020)en)index+html/
0

2rom 3enner to 'asteur to #illeman

%solate %nactivate %n&ect the
microorganism causing disease

uring the last 30 !ears, several ne* technologies made possible vaccines that *ere previousl! impossible

uring the last 30 !ears, several ne* technologies made possible vaccines that *ere previousl! impossible

'eningococcal disease

(aused b) Neisseria meningitidis capsular serogroups *,

B, (, +, ,1-

Death

Severe disability

reaming the ol!mpic games li4e 'istorius

Tragedies covered by media

uring the last 30 !ears, several ne* technologies made possible vaccines that *ere previousl! impossible

5on6ugate vaccines

(apsular pol)sacc!arides . (on&ugates

#aemophilus influen,ae t!pe 7 8#ib/

5apsule
'neumococcus

5apsule

Meningococcus

'ol!saccharide

%roup 7 streptococcus

5on6ugate

Men5 5on6ugate .accine 8red/ Induced high level of 7actericidal &ntibodies in Infants+ 'lain 'ol!saccharide 8blue/ *as a poor Immunogen

(on&ugate vaccines for 'eningococcus ( eliminated t!e disease in t!e U/

9aborator! 5onfirmed 5ases of :erogroup 5 Meningococcal 8;ngland < "ales/

isease

:ince the introduction of the >? Men5 vaccine in 1@@@ .accine

>1-,000 cases prevented

A 1,300 deaths prevented A2,710 permanent seBuelae prevented

,ee0 1o2 8totals from mid=!ear/

Meningococcus 7 capsule is a self antigen and cannot be used for vaccination

uring the last 30 !ears, several ne* technologies made possible vaccines that *ere previousl! impossible

Reverse Vaccinolog)

a genomic approach to vaccine discovery

Ceverse vaccinolog!

;xpress recombinant proteins

D00 potential vaccine candidates identified 310 proteins successfull! expressed in ;+coli

In silico vaccine candidates

@1 novel surface=exposed proteins identified 20 novel proteins have bactericidal activit!

VACCINE CANDIDATES

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/

54S

6'V
f#7' Ead& E#7&

4or*

(lass 3

(lass 4orB

45Men7 is a suspension for in6ection

Dose 0.5ml NHBAGNA1030

fHbpGNA2091

NadA 50 g

OMV 25 g

Al3+ 0.5 mg

50 g

50 g

(linical 7evelopment
Immunogenicity, Persitance, Concomitant administration, Tolerability

%nfants and c!ildren " mont!s to 8" )ears of age

G 9 0 received at least 1 dose of
7;H:;C$ G3201 received booster dose in second !ear of life

9 0

(!ildren " to 10 )ears of age

G" 0 *ere included

" 0

170-

*dolescents and adults :11 )ears of age

G

170- *ere included

I;valuated in 13 studies including @ randomi,ed controlled clinical trials+

'enB Vaccine U/ media

5#M' positive opinion
1D Eovember 2012

To*ards a meningitis free *orld

The first vaccine lot *as released this *ee4 Eo* *e can eliminate meningococcal meningitis

Ceverse vaccinolog! allo*ed us to target man! pathogens that *ere difficult or impossible before Including SUPER U!S

45Men7 first genome derived

vaccine

## # # t n a t s si us e r c cocc i t o i b lo i i t y n h l " p Sta E$ co cile %i nas % i d C$ omo ud e s P

# # # S ! U R E P U S

;roup B Streptococcus +ersinia pestis

;roup * Streptococcus

'alaria

(!lam)dia

uring the last 30 !ears, several ne* technologies made possible vaccines that *ere previousl! impossible

&d6uvants

M21@( oil=in=*ater ad6uvant licensed *ith seasonal trivalent 81@@7/ and pandemic monovalent vaccine
Progenitor of other oil-in-water based adjuvants
6il#in#$ater emulsion ad&uvant licensed for use in seasonal influenza vaccine <5U*7@ since 1==7
G &ore than '(( million

1D0nm

commercial doses distributed

oil

)*'( Clinical studies, )'((,((( sub+ects

G No sa%ety signals in either Sa%ety
'< = ad&uvant emulsion

sho,n also in pregnant ,omen

*ntigens S4*1 9 >,??1 90

Pediatric studies and e%%icacy trial in )-,((( sub+ects

5icensed for "00= *AB111C pandemic vaccine Aall agesC

M21@ increases efficac! of influen,a vaccine in children from 43 to 0DJ

@ 21 M K

120 029

cci .a

ne

Vaccine efficac) vs2 non#influenza control

02E 023 02" 020 D 02" D 023 D 02E 0 "0 30 E0 90 100 1"0 130 1E0

cci a .

ne

<luad >%V
190 "00 ""0

.accine also sho*ed satisfactor! safet! profile( GIncreased local reactogenicit! GEo increase in serious adverse experiences vs+ control

7a)s post#second dose

Vesi0ari >, et al$ 1?F'2

uring the last 30 !ears, several ne* technologies made possible vaccines that *ere previousl! impossible

S)nt!etic biolog)
:!nthetic seeds :elf &mplif!ing
Messenger CE& 8S*'C

%nfluenza, eggs . cell culture

time to retire the eggsL

TechnoIog! of 1@30Ms

5ell culture, licensed b! the 2 & in 2012

& s!nthetic Influen,a .accine :eed in 1 da!s

shipping information instead of viruses

uring the last 30 !ears, several ne* technologies made possible vaccines that *ere previousl! impossible

"hat do *e do *ith all these technologiesL

.accines have been developed for children

With 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+1030)nri3001

Vaccines for ever) age

R.Rappuoli, C. andl, !" #lac$ , %. &e 'regorio (ature Reviews Immunology N Eovember 2011O doi(10+1030)nri3001

&n Institute to address the gaps in vaccine development

.accines against povert!

In the recent past, no mechanism ,as in place to develop vaccines needed only in developing countries

1ovartis Vaccines %nstitute for ;lobal Bealt! A1V;BC

& ne* non#profit initiative to develop effective and affordable vaccines for neglected infectious diseases of developing countries
9ocated in :iena , Ital! 9egal entit! started in 2eb 2007 &llan :aul hired as 5;$ :ept 2007 Inauguration
2eb 22, 2000 >)p!oid vaccine licensed to Bio? post p!ase %%, Fune "01-

Master Program in Vaccinology & Pharmaceutical Clinical Development :

G)as reached so far *+ countries of the developing world G70J of the former students are activel! *or4ing in the vaccinolog! field G2ormer students are follo*ed for 1 !

Fobs, investments, brains

1=="
Fobs 234

"00E
1100

"012000

%nvestments %nvestments in R.7

======200M===== =====0@0M=====

4eople 41J of our collaborators are *omen 41J are graduated emplo!ees 40J are less than 31 !ears old 5ollaborators come from 43 different countries