Full Te ms & Condi ions o access and use can be ound a
h p://www. and online.com/ac ion/jou nalIn o ma ion?jou nalCode=kh i20
Download by: [Tampe e Uni e si y] Da e: 17 No embe 2016, A : 03:25
Human Vaccines & Immuno he apeu ics
ISSN: 2164-5515 (P in ) 2164-554X (Online) Jou nal homepage: h p://www. and online.com/loi/kh i20
F om ubella o o a i us, and beyond
Timo Vesika i
To ci e his a icle: Timo Vesika i (2015) F om ubella o o a i us, and beyond, Human
Vaccines & Immuno he apeu ics, 11:6, 1302-1305, DOI: 10.1080/21645515.2015.1051404
To link o his a icle: h p://dx.doi.o g/10.1080/21645515.2015.1051404
© 2015 The Au ho (s). Published wi h
license by Taylo & F ancis G oup, LLC©
Timo Vesika i
Published online: 18 Jun 2015.
Submi you a icle o his jou nal
A icle iews: 226
View ela ed a icles
View C ossma k da a
F om ubella o o a i us, and beyond
Timo Vesika i*
Vaccine Resea ch Cen e ; Uni e si y o Tampe e; Tampe e, Finland
I was cus oma y o medical s uden s
wi h some ambi ion o seek hei way o a
biomedical esea ch g oup. I was in igued
by i uses, and i ology was one o he
ew subjec s in medical school ha I s ud-
ied wi h eal in e es . Nex , in la e 1966, I
was inc edibly lucky o mee An i Vahe i
(la e P o esso o Vi ology) who had jus
e u ned o Finland om he Wis a Ins i-
u e in Philadelphia wi h all he la es
knowledge in ubella esea ch. Rubella
i us hemagglu ina ion had been disco -
e ed and wi h hemagglu ina ion inhibi-
ion (HI) es a ailable I was soon unning
a diagnos ic ubella labo a o y which no
only p o ided ma e ial o esea ch bu
also c ea ed eal income o he Depa -
men and ou g oup. This se a p eceden
o my la e p o essional li e. G an s a e
good bu i is be e i he esea ch unding
can be ob ained om ou side.
We de eloped he i s ubella IgM es
o he diagnosis o ecen in ec ion by
sepa a ing he 19S (IgM) and 7S (IgG)
an ibodies using ul acen i uga ion and
es ing he ac ions using HI es . This
was he mo he o all IgM an ibody diag-
nos ics, and became a Ci a ion Classic by
Cu en Con en s. The ubella IgM es
also opened he doo o my la e wo k in
New Yo k, in D . Louis Z. Coope ’s (o ig-
inally P o esso Saul K ugman’s) Rubella
P ojec in he yea s 1972–1975. Bu
be o e his I made my i s con ac wi h
accine esea ch.
Li e a enua ed ubella accines we e
being de eloped and he leading candida e
was HPV-77 high passage i us om
NIH. An impo an open ques ion was
whe he he li e a enua ed accine would
c oss placen a same way as wild ype
ubella i us. The c ucial s udy was o be
done in Finland, away om po en ially
damaging publici y in he US, wi h D .
F ed Robbins, a Nobel Lau ea e, as he
god a he o he p ojec . Unde he senio s
I was o do much o wo k: accina e p eg-
nan women p esc eened o be se onega-
i e o ubella and scheduled o ha e a
legal abo ion a week o wo la e . The
plan was o isola e ubella ( accine) i us
om he p oduc s o concep ion and, in
ac , we succeeded in doing ha .
Consequen ly I go an oppo uni y o
a end an in e na ional con e ence on
ubella accina ion in Be hesda, MD, in
Feb ua y 1969. This was an eye opene in
many ways. I quickly ealized ha accine
esea ch was as much abou science as i
was abou poli ics. The mos imp essi e
spec acle o he con e ence was S anley
Plo kin’s p esen a ion on he RA 27/3
candida e ubella accine g own in WI-38
human ib oblas cells. By all accoun s,
immunogenici y and sa e y, RA 27/3
appea ed supe io o HPV77 and i s
de i a i es, bu he numbe o case his o-
ies o accina ed subjec s ell sho o he
equi ed 5000 and he licensu e o he
“o icial candida e” HPV77 was on i s
way. The unholy alliance o NIH and
Me ck had done e e y hing o he
HPV77/DE5 ( i e passages in duck
emb yo cells a Me ck) accine o be eady
o licensu e in May 1969, wi h millions
o doses al eady p oduced o sa u a e he
ma ke immedia ely. As a oken sign o
open compe i ion also a Belgian accine,
Cendehill s ain by Jan Desmy e , was
g an ed licensu e, bu had no eal chance
in he US ma ke . - As an epilogue,
RA27/3 was la e adop ed by Me ck and
o he manu ac u e s in 1978 o be
included in MMR accine.
My ime in New Yo k in 1972–1975,
i s wi h New Yo k Uni e si y o a he Bel-
le ue Hospi al and hen a he Roose el
Hospi al a ilia ed wi h Columbia was highly
in e es ing, pleasu able and educa ional, bu
no e y p oduc i e as I was p e y much
© Timo Vesika i
*Co espondence o: Timo Vesika i; Email: imo.
esika i@u a.fi
h p://dx.doi.o g/10.1080/21645515.2015.1051404
This is an Open Access a icle dis ibu ed unde he
e ms o he C ea i e Commons A ibu ion-Non-
Comme cial License (h p://c ea i ecommons.o g/
licenses/by-nc/3.0/), which pe mi s un es ic ed
non-comme cial use, dis ibu ion, and ep oduc ion
in any medium, p o ided he o iginal wo k is p op-
e ly ci ed. The mo al igh s o he named au ho (s)
ha e been asse ed.
1302 Volume 11 Issue 6Human Vaccines & Immuno he apeu ics
Human Vaccines & Immuno he apeu ics 11:6, 1302--1305; June 2015; Published wi h license by Taylo & F ancis G oup, LLC
PORTRAIT
alone unning a small labo a o y. I lea ned a
lo abou cell-media ed immuni y, hen a
new and eme ging a ea. I men o ed a hesis
wo k o a isi ing scien is , G€ule Kan a, and
made a li elong iendship wi h he u u e
P o esso o Pedia ics a Hace epe Uni e -
si y in Anka a, wi h equen connec ions o
Tu key. Ano he long-las ing iendship was
wi h my echnician Tom By ne. I will always
emembe hismaxim“ hisissosimple ha
e en a doc o can do i ”. I lea ned o app eci-
a e many hings in he US, i s o all ha he
eminen posi ion in science was based on
ha d wo k and long hou s, which I o en
men ion o younge colleagues in Finland.
On my e u n o Finland ubella was
no longe a ho opic. I did my pedia ic
esidency and eached o new opics. In
he new medical school o he Uni e si y
o Tampe e we lea ned abou he ecen ly
disco e ed o a i us and s a ed doing
diagnos ic wo k using elec on mic oscopy
in 1976. The nex yea oge he wi h
Ma kku M€aki (la e P o esso o Pedia -
ics) we s a ed a p ospec i e su eillance
on he e iology o acu e gas oen e i is in
child en and ound ou ha o a i us was
esponsible o 54% o hospi al admis-
sions and he o a i us season was om
Decembe o June. This in o ma ion was
essen ial o he i s o a i us accine e i-
cacy ial.
I had me F ancis And e in 1977, and
we became good iends un il his passing ,
in 2014. F ancis was he Scien i ic and
Medical Di ec o o a Belgian company
RIT, la e o become Smi hKline-RIT,
SB, and inally GSK. The CEO o he
company was S an Huygelen, a e e ina -
ian, who had in e es in animal diseases
and had acqui ed a cal o a i us s ain
NCDV o passaging in cell cul u e
(human o a i us could no be g own
hen) and o e en ual de elopmen as a
e e ina y accine. Bu he e was also
c oss- eac i i y be ween human and ani-
mal g oup A o a i uses. Geo ge Zissis
es ed he NCDV, now designa ed as
RIT4237, in gno obio ic pigs and ound
ha p e ious adminis a ion o he
“ accine” p o ec ed agains challenge by
wo human o a i uses.
The nex logical hing o do was o
s a human s udies. F ancis And e ga e
us some doses o RIT4237 o gi e o
human adul olun ee s, including swal-
lowing i mysel . The e we e no symp-
oms, bu he e was no much o an
immune esponse ei he , due o p e-exis -
ing an ibodies. We p oceeded o child en
and obse ed immune esponses bu s ill
no symp oms. Encou aged, we wen on o
a quick (no di y) e icacy ial in 8–11
mon h-old in an s o RIT4237 one dose
s. placebo wi h ollow-up om Janua y
o May 1983. When analyzing he da a
wi h my younge colleague E ika Isolau i
(la e P o esso o Pedia ics he sel ), we
no iced ha we had ewe cases in he ac-
cina ed g oup, bu he esul s we e clea e
when we looked a he clinical p esen a-
ion o he cases so ha we in oduced he
e m “clinically signi ican dia hea”, and
agains his end poin he accine had
Abou D Vesika i
D Timo Vesika i ob ained his MD and PhD in Medical Sciences om Uni e si y o Helsinki in Finland
in 1969 and 1972, espec i ely. F om 1972-1975 he pe o med pos doc o al s udies in New Yo k a
Belle ue Hospi al and Roose el Hospi al.
His appoin men s a Uni e si y o Tampe e include P o esso o Pedia ics in 1981-7 and P o es-
so o Vi ology in 1991-2012, and he was Di ec o o i s Medical School in 1995-2001, whe e he
se es as Di ec o o he Vaccine Resea ch Cen e . D Vesika i wo ked wi h he Dia heal Disease
Con ol P og am o he Wo ld Heal h O ganiza ion (WHO) in 1987-90 and subsequen ly se ed on
WHO S ee ing Commi ees on Dia heal Disease Vaccines and on Epidemiology and Field Resea ch.
D . Vesika i’s esea ch in e es has ocused on accine s udies since he fi s ubella accine ial
in Finland in 1968. F om he 1980’s o p esen he pe o med esea ch on a icella accines, bu his
majo in e es o e he pas 30 yea s has been o a i us dia hea and accine. He conduc ed he
fi s clinical ials o li e o al o a i us accines in humans in 1982-3, ollowed by se e al o he o a-
i us candida e accines. He con inued o wo k wi h he ecen o a i us accines o GSK and
Me ck, being he p incipal in es iga o o he fi s pedia ic ials o Ro a ix accine and he lead
in es iga o o he Me ck’s Ro aTeq accine ial REST, wi h o e 70.000 subjec s en olled in Finland
and he US. D . Vesika i has conduc ed clinical ials on many o he accines o child en, including
li e a enua ed and adju an ed inac i a ed influenza accines, MMRV accines, pneumococcal con-
juga e accines and meningococcal accines.
Du ing he cou se o his ca ee D Vesika i published abou 300 a icles in pee - e iewed jou nals,
mo e han hal o which we e on dia heal diseases and o a i us accine. In 2007 D Vesika i
ecei ed he Lance ’s“Pape o he Yea ”awa d o he publica ion o he Ro a ix and Ro aTeq
Phase 3 ial da a.
D Vesika i is an ac i e membe o many na ional and in e na ional socie ies and councils. In 1990
he was Bill Ma shall lec u e o he Eu opean Socie y o Pedia ic In ec ious Diseases (ESPID), and in
2004 o ganized he ESPID Mee ing in Tampe e. D Vesika i has se ed on ad iso y boa ds o se e al
companies, including Me ck, GSK, SanofiPas eu , No a is and MedImmune. He has also helped o
o ganize se e al Eu opean Expe Mee ings on Ro a i us Vaccina ion, and is egula ly in i ed o
p esen a na ional and in e na ional accine con e ences.
www. and online.com 1303Human Vaccines & Immuno he apeu ics
con e ed 90% p o ec ion. - La e , wi h
Ta ja Ruuska, we de ised a nume ical
sco e o assess clinical se e i y mo e objec-
i ely. This has become known as
“Vesika i sco e”, and many people know
my name om i .
Iknewwehadsome hinggoodand
impo an a hand,akindo i s in he
wo ld. Wi h F ancis And ewedesigned17
p o ocols o which 10 we e ca ied ou in
Tampe e, Finland, in he nex h ee yea s, o
co e all a eas o o a i us accine, and we
p e y much succeeded in lea ning mo e
abou o a i us accine and accina ion han
o he s ound in he nex 15 yea s. The idea
was, is-a- iz he ubella accine expe ience,
o succeed his ime and ha e a Eu opean
accine licensed and used.
Re iewing wha happened helps o
unde s and how he a i udes ha e
changed. In Eu ope, he main obs acle was
lack o da a: he signi icance o o a i us
disease was no much known o app eci-
a ed ou side Finland, and ew people o
coun ies we e in e es ed in he accine. As
i has u ned ou o be in he 2000’s, e e y
coun ywillneed odoi sownepidemiol-
ogy and heal h economics be o e conside -
ing a new accine, such as o a i us.
Globally, he ecep ion by he WHO
came as a disappoin men . The a i ude o
he WHO’s Dia hoeal Disease Con ol
(CDD) P og amme was gene ally nega-
i e. I was only la e ha I ealized he
eason was ha ou s was he w ong ac-
cine. The Ame ican domina ed CDD was
de e mined o supp ess a Eu opean ac-
cine o pa e way o US compe i o s
which we e o hcoming bu la e. The
ci ed easons we e, among o he hings
ha he accine should be 100% e ica-
cious agains all o a i us dia hea and no
only e icacious agains se e e disease – an
un ealis ic equi emen ha no o a i us
accine has me o will e e mee . The
accine should also be e icacious in de el-
oping coun ies – a easonable equi e-
men , which ac ually was me i se e e
o a i us dia hea was he end poin . E en
i RIT4237 accine was no pe ec i was
easy o p oduce and could ha e made a
big di e ence i in oduced in he la e
1980’s. I s ill eel sad abou hinking how
many li es could ha e been sa ed o e
wen y yea s o so i he i s o al o a i us
accine had been pu in ield use wi h he
same igo as o al ehyd a ion solu ion in
hose imes.
I joined he WHO CDD P og amme
o a couple o yea s (1987–1990). The
expe ience was mixed. I was g ea o ha e
oppo uni y o a eling he hen exo ic
coun ies and wo k on a ious s udies.
Mos o my connec ions wi h de eloping
coun ies in Asia and also La in Ame ica
a e om ha ime. Wi hin he o ganiza-
ion, i was disappoin ing o see how li le
academic esea ch o c eden ials ea ned in
esea ch we e app ecia ed. When he
CDD P og amme was unning ou s eam
and mos o unding i was ime o lea e.
A e my e u n o Finland I became
P o esso o Vi ology and e ained my
posi ion as a Head o Pedia ic In ec ious
Diseases a he Tampe e Uni e si y Hos-
pi al. I like o call mysel wi h a line bo -
owed om Luis A enda~no (who wo ked
o a ime a NIH), “The bes i ologis
among pedia icians and he bes pedia i-
cian among i ologis s”.
Fo a qua e o cen u y I ha e been a
p oponen o o a i us accina ion in a
gene ic way, wo king wi h all accines and
accine manu ac u e s. I had a good wo k-
ing ela ionship wi h Wye h on Ro a-
Shield accine, al hough I always
complained abou i s high eac ogenici y
(in ussuscep ion was no ye known).
Toge he wi h he accine’s de elope , Al
Kapikian o NIH, we conduc ed a s udy
on neona al adminis a ion o Ro aShield
and showed ha a his age he accine
was sa e. Neona al accina ion was suc-
cess ully applied in a ecen s udy in
Ghana, in an a emp o esu ec he
Ro aShield accine o use in de eloping
coun ies a e wi hd awal in 1999 o
in ussuscep ion. I wo ked wi h Al Kapi-
kian on his p ojec un il his dea h in
2014. My ad ice o Wye h in he ea ly
1990’s was o launch hesus-based Ro a-
Shield i s as a empo a y solu ion bu
eplace i la e wi h a bo ine-human eas-
so an accine (also de eloped a NIH),
which un o una ely did no happen.
Collabo a ion wi h Me ck on hei
bo ine-human easso an accine
Ro aTeqÒ, speci ically ca ying ou a majo
po ion o he REST s udy, occupied se -
e al yea s o almos ull- ime ac i i y, and
was g a i ying as his accine was e en ually
licensed in 2006. The publica ion o he
REST s udy was also a majo miles one as i
he alded he new coming o o a i us acci-
na ion wi h wo new accines, Ro aTeqÒ
and he human o a i us accine Ro a ixTM
by GSK. I also wo ked on he la e since i s
i s clinical p o ocol in 2000.
TheRESTs udyenabledme oes ablish
a ne wo k o accine ial clinics a ound Fin-
land. The ne wo k, collec i ely pa o he
Vaccine Resea ch Cen e o he Uni e si y o
Tampe e, is now well known among accine
manu ac u e s. In addi ion o Me ck and
GSK,Iha ewo kedwi hSano iPas eu ,
SP-MSD, No a is, P ize , Bax e , MedI-
mmune and o he s (some companies no lon-
ge exis ) and he accines ha e included
in luenza, a icella, zos e , MMR-V, pneu-
mococcal conjuga e, meningococcal ac-
cines, hexa alen combina ion accines, and
many o he s. Since abou 2000, I ha e been
mo e o less a p o essional accinologis . In
gene al, he ela ionship wi h indus y has
wo ked well bo h ways. I is g a i ying o be
he Lead In es iga o o good accines and
see hei way o licensu e and implemen a-
ion wi h ac ual impac and bene i o chil-
d en. In addi ion o o a i us, such
accines include a icella accine, in anasal
in luenza accine and meningococcal g oup
B accine. Recip ocally, many accine man-
u ac u e s ha e p obably bene i ed om
close collabo a ion and communica ion
wi h an expe ienced academic in es iga o .
A leas his is how i was un il ecen ly
when la ge mul ina ional CRO companies
ha e been ou sou ced o do much o clini-
cal accine esea ch o he manu ac u e s,
by which he genuine wo-way communi-
ca ion has su e ed.
The clinical accine ial o ganiza ion
wi hin he Uni e si y has o e he yea s
c ea ed su plus which I ha e been able o
use o esea ch. The Vaccine Resea ch
Cen e has included labo a o y compo-
nen o o e 20 yea s. In he 1990’s wi h
Xiao-Li Pang we disco e ed ha no o i-
uses we e a signi ican cause o acu e gas-
oen e i is in child en, ac ually mo e
common han o a i uses i mild cases
we e coun ed. This was he backg ound
o he gene al idea o accina ing young
child en agains no o i uses.
Since he licensu e o o al o a i us
accines in 2006 we ha e been wo king
on non-li e o a i us accine and no o i-
us accines, p e e ably in combina ion.
1304 Volume 11 Issue 6Human Vaccines & Immuno he apeu ics
While I do no do ac i e labo a o y wo k
wi h my own hands any mo e, I ha e a
nice g oup o in es iga o s supe ised by
Vesna Blaze ic, a close cowo ke . The no -
o i us componen s o he accine a e
based on i us like pa icles (VLPs). The
o a i us componen is VP6 p o ein
which, when p oduced in baculo i us-
insec cell sys em, sel assembles o o m
small od-like s uc u es. VP6 is my old
obsession since he ea ly accine ials in
he 1980’s, when Lenna S ensson
showed om ou pos - accina ion se a
ha mos o he an ibody esponse was
agains VP6, an an igen which was no
app ecia ed because he an ibodies aised
agains i we e non-neu alizing. I now
appea s ha VP6 alone may ac ually
induce p o ec i e immuni y.
Now ha I am e i ed om my p o es-
so ship and no longe engaged in eaching
o hospi al wo k I am ac ually able o
de o e mo e ime o esea ch han be o e.
I ce ainly hope o emain ac i e in he
coming yea s o be able o ca y h ough
clinical ials o ou no o i us VLP – o a-
i us VP6 combina ion accine.
My zodiac is Gemini. In my p o essional
li e I ha e always had wo sides, like basic
and clinical esea ch, o i ology and pedia -
ics. The balance may ha e il ed a imes,
bu I ha e always been happy o ha e bo h
o hem, and he eeling is only ein o ced
when I alk o my colleagues who a e locked
in one subjec only. Some imes he cou se
o e en s has no been clea a once. I had
mixed eelings in 1975 on e u n om New
Yo k o Tampe e, o his new Medical
School wi h insu icien acili ies, bu hen
in a ew yea s ealized ha luck had been on
my side. I was able o s a a signi ican
ca ee in pedia ics, which in u n opened
en i ely new a enues o me. Likewise, he
e u n in 1990 om Gene a o Finland was
a jump o some unce ain y, bu hen again
u ned ou o be a s ike o luck as I could
ob ain a ailo made posi ion combining
i ology and pedia ics, leading o he c ea-
ion o Vaccine Resea ch Cen e and a new
balance be ween clinical and basic. A com-
o able posi ion.
www. and online.com 1305Human Vaccines & Immuno he apeu ics