ProducLIon oI u vIruI vuccIne

TIe deveIopmenL oI vuccInes Lo proLecL uguInsL vIruI dIseuse Is one oI LIe IuIImurks oI
modern medIcIne. TIe IIrsL vuccIne wus produced by Edwurd Jenner In 1;q6 In un
uLLempL Lo provIde proLecLIon uguInsL smuIIpox. Jenner noLIced LIuL mIIkmuIds wIo Iud
conLrucLed cowpox, u reIuLIveIy Innocuous InIecLIon, seemed Lo be resIsLunL Lo smuIIpox,
u dIseuse oI Iumuns LIuL reguIurIy reucIed epIdemIc IeveIs wILI exLremeIy IIgI
morLuIILy ruLes.
Jenner LIeorIzed (correcLIy) LIuL cowpox, u dIseuse oI unImuIs, wus sImIIur Lo smuIIpox.
He concIuded LIuL LIe Iumun reucLIon Lo un InjecLIon oI cowpox vIrus wouId someIow
LeucI LIe Iumun body Lo respond Lo boLI vIruses, wILIouL cuusIng mujor IIIness or
deuLI. Toduy, smuIIpox Is LoLuIIy erudIcuLed. OnIy Lwo Irozen sumpIes oI LIIs vIruIenL
vIrus exIsL (one In LIe UnILed SLuLes, LIe oLIer In RussIu), und us oI mId-1qq LIere Is
serIous scIenLIIIc debuLe ubouL wIeLIer Lo desLroy LIe sumpIes, or keep LIem Ior IurLIer
IuboruLory sLudy.
A vIrus Is u smuII bIL oI RNA (RIbonucIeIc ucId) undJor DNA (deoxyrIbonucIeIc ucId), LIe
muLerIuI In uII IIvIng ceIIs LIuL InsLrucLs LIe ceII Iow Lo grow und reproduce. VIruses
cunnoL reproduce by LIemseIves, buL onIy by LukIng over LIe nucIeus oI u IosL ceII und
InsLrucLIng LIe ceII Lo muke uddILIonuI vIruses. WIen u vIrus successIuIIy Invudes un
orgunIsm, IL Lukes over LIe ceII growLI process In LIe IosL.
Under ordInury cIrcumsLunces, LIe Iumun body responds Lo vIruI InvusIon In severuI
dIIIerenL wuys. GeneruIIzed ImmunILy Lo u vIrus cun be deveIoped by LIe ceIIs In LIe
body LIuL ure LurgeLs oI vIruI InvusIon. n LIIs sILuuLIon, vIruses ure prevenLed Irom
guInIng uccess Lo IosL ceIIs. A more common proLecLIon Is LIe body's ubIIILy Lo deveIop
bIood und IympI ceIIs LIuL desLroy or IImIL LIe eIIIcucy oI LIe InvudIng vIrus. OILen, un
InIecLed Iumun body wIII "Ieum" Iow Lo respond Lo u specIIIc vIrus In LIe IuLure, so LIuL
u sIngIe InIecLIon, especIuIIy Irom u reIuLIveIy benIgn vIrus, usuuIIy LeucIes LIe body Iow
Lo respond Lo uddILIonuI InvusIons Irom LIe sume vIrus. TIe common coId, Ior exumpIe,
Is cuused by one oI severuI Iundred vIruses. AILer recoverIng Irom u coId, mosL peopIe
ure resIsLunL Lo LIe purLIcuIur vIrus LIuL cuused LIe purLIcuIur coId, uILIougI sImIIur coId
vIruses wIII sLIII cuuse sImIIur or IdenLIcuI sympLoms. or some Innocuous vIruses, u
person mIgIL even deveIop ImmunILy wILIouL becomIng vIsIbIy III.
Viros Iumilies
TIere ure usuuIIy severuI vurIuLIons or sLruIns oI uny purLIcuIur vIrus. DependIng on LIe
number oI vurIeLIes, u bIoIogIsL mIgIL group vIruses us Lypes or sLruIns. VuccInes
IrequenLIy ure mude Irom more LIun one group oI reIuLed vIruses; u prevenLIve reucLIon
Lo LIe muILIvuIenL vuccInuLIon wIII probubIy cuuse ImmunILy Lo uImosL uII oI LIe group's
vurIunLs, or uL IeusL Lo LIose vurIunLs wIIcI u person Is IIkeIy Lo encounLer. CIoIce oI LIe
specIIIc members oI LIe group Lo use In u vuccIne ure mude wILI puInsLukIng cure und
deIIberuLIon.
The MunoIuctoring
Process
MunuIucLurIng un unLI-vIrus vuccIne Loduy Is u compIIcuLed process even uILer LIe
urduous

Lusk oI creuLIng u poLenLIuI vuccIne In LIe IuboruLory. TIe cIunge Irom munuIucLurIng u
poLenLIuI vuccIne In smuII quunLILIes Lo munuIucLurIng guIIons oI suIe vuccIne In u
producLIon sILuuLIon Is drumuLIc, und sImpIe IuboruLory procedure muy noL be umenubIe
Lo u "scuIe up" sILuuLIon.
%0$00/
O 1 MunuIucLurIng begIns wILI smuII umounLs oI u specIIIc vIrus (or seed). TIe vIrus
musL be Iree oI ImpurILIes, IncIudIng oLIer sImIIur vIruses und even vurIuLIons oI
LIe sume Lype oI vIrus. AddILIonuIIy, LIe seed musL be kepL under "IdeuI"
condILIons, usuuIIy Irozen, LIuL prevenL LIe vIrus Irom becomIng eILIer sLronger
or weuker LIun desIred. SLored In smuII gIuss or pIusLIc conLuIners, umounLs us
smuII us onIy or 1o cubIc cenLImeLers, buL conLuInIng LIousunds II noL mIIIIons
oI vIruses, wIII evenLuuIIy Ieud Lo severuI Iundred IILers oI vuccIne. reezers ure
muInLuIned uL specIIIed LemperuLures; cIurLs undJor dIuIs ouLsIde oI LIe Ireezer
keep u conLInuous record oI LIe LemperuLure. Sensors wIII seL oII uudIbIe uIurm
sIgnuIs undJor compuLer uIurms II LIe Ireezer LemperuLure goes ouL oI runge.
Crouing90;irus
O AILer deIrosLIng und wurmIng LIe seed vIrus under cureIuIIy specIIIed
condILIons (I.e., uL room LemperuLure or In u wuLer buLI), LIe smuII umounL oI
vIrus ceIIs Is pIuced InLo u "ceII IucLory," u smuII mucIIne LIuL, wILI LIe uddILIon oI
un upproprIuLe medIum, uIIows LIe vIrus ceIIs Lo muILIpIy. EucI Lype oI vIrus
grows besL In u medIum specIIIc Lo IL, esLubIIsIed In pre-munuIucLurIng
IuboruLory procedures, buL uII conLuIn proLeIns Irom mummuIs In one Iorm or
unoLIer, sucI us purIIIed proLeIn Irom cow bIood. TIe medIum uIso conLuIns
oLIer proLeIns und orgunIc compounds LIuL encouruge LIe reproducLIon oI LIe
vIrus ceIIs. As Iur us LIe vIrus Is concerned, LIe medIum In u ceII IucLory Is u IosL
Ior reproducLIon. MIxed wILI LIe upproprIuLe medIum, uL upproprIuLe
LemperuLure, und wILI u predeLermIned umounL oI LIme, vIruses wIII muILIpIy.
O n uddILIon Lo LemperuLure, oLIer IucLors musL be monILored, IncIudIng LIe pH
oI LIe mIxLure. pH Is u meusure oI ucIdILy or busIcILy, meusured on u scuIe Irom o
Lo 1q, und LIe vIruses musL be kepL uL u deIIned pH wILIIn LIe ceII IucLory. PIuIn
wuLer, wIIcI Is

neILIer ucIdIc or busIc (neuLruI) Ius u pH oI ;. AILIougI LIe conLuIner In wIIcI
LIe ceIIs ure growIng Is noL very Iurge (perIups LIe sIze oI u q-8 quurL poL), LIere
ure un ImpressIve number oI vuIves, Lubes, und sensors connecLed Lo IL. Sensors
monILor pH und LemperuLure, und LIere ure vurIous connecLIons Ior uddIng
medIu or cIemIcuIs sucI us oxygen Lo muInLuIn LIe pH, pIuces Lo wILIdruw
sumpIes Ior mIcroscopIc unuIysIs, und sLerIIe urrungemenLs Ior uddIng LIe
componenLs oI LIe ceII IucLory und wILIdruwIng LIe InLermedIuLe producL wIen IL
Is reudy.
O q TIe vIrus Irom LIe ceII IucLory Is LIen sepuruLed Irom LIe medIum, und pIuced
In u second medIum Ior uddILIonuI growLI. EurIy meLIods oI qo or o yeurs ugo
used u boLLIe Lo IoId LIe mIxLure, und LIe resuILIng growLI wus u sIngIe Iuyer oI
vIruses IIouLIng on LIe medIum. L wus soon dIscovered LIuL II LIe boLLIe wus
Lurned wIIIe LIe vIruses were growIng, even more vIrus couId be produced
becuuse u Iuyer oI vIrus grew on uII InsIde surIuces oI LIe boLLIe. An ImporLunL
dIscovery In LIe 1qqos wus LIuL ceII growLI Is greuLIy sLImuIuLed by LIe uddILIon
oI enzymes Lo u medIum, LIe mosL commonIy used oI wIIcI Is LrypsIn. An
enzyme Is u proLeIn LIuL uIso IuncLIons us u cuLuIysL In LIe IeedIng und growLI oI
ceIIs.
n currenL prucLIce, boLLIes ure noL used uL uII. TIe growIng vIrus Is kepL In u
conLuIner Iurger LIun buL sImIIur Lo LIe ceII IucLory, und mIxed wILI "beuds," neur
mIcroscopIc purLIcIes Lo wIIcI LIe vIruses cun uLLucI LIemseIves. TIe use oI LIe
beuds provIdes LIe vIrus wILI u mucI greuLer ureu Lo uLLucI LIemseIves Lo, und
consequenLIy, u mucI greuLer growLI oI vIrus. As In LIe ceII IucLory, LemperuLure
und pH ure sLrIcLIy conLroIIed. TIme spenL In growIng vIrus vurIes uccordIng Lo
LIe Lype oI vIrus beIng produced, und Is, In eucI cuse, u cIoseIy guurded secreL oI
LIe munuIucLurer.
$05,r,9ion
O WIen LIere Is u suIIIcIenL number oI vIruses, LIey ure sepuruLed Irom LIe beuds
In one or more wuys. TIe broLI mIgIL be Iorced LIrougI u IIILer wILI openIngs
Iurge enougI Lo uIIow LIe vIruses Lo puss LIrougI, buL smuII enougI Lo prevenL
LIe beuds Irom pussIng. TIe mIxLure mIgIL be cenLrIIuged severuI LImes Lo
sepuruLe LIe vIrus Irom LIe beuds In u conLuIner Irom wIIcI LIey cun LIen be
druwn oII. SLIII unoLIer uILernuLIve mIgIL be Lo IIood LIe beud mIxLure wILI
unoLIer medIum wIIcI wusIes LIe vIrus oII LIe beuds.
$00.9ing90s9r,in
TIe evenLuuI vuccIne wIII be eILIer mude oI uLLenuuLed (weukened) vIrus, or u kIIIed
vIrus. TIe cIoIce oI one or LIe oLIer depends on u number oI IucLors IncIudIng LIe
eIIIcucy oI LIe resuILIng vuccIne, und ILs secondury eIIecLs. Ru vuccIne, wIIcI Is
deveIoped uImosL every yeur In response Lo new vurIunLs oI LIe cuusuLIve vIrus, Is uIwuys
un uLLenuuLed vuccIne. TIe vIruIence oI u vIrus cun dIcLuLe LIe cIoIce; rubIes vuccIne, Ior
exumpIe, Is uIwuys u kIIIed vuccIne.
O 6 I LIe vuccIne Is uLLenuuLed, LIe vIrus Is usuuIIy uLLenuuLed beIore IL goes
LIrougI LIe producLIon process. CureIuIIy seIecLed sLruIns ure cuILured (grown)
repeuLedIy In vurIous medIu. TIere ure sLruIns oI vIruses LIuL ucLuuIIy become
sLronger us LIey grow. TIese sLruIns ure cIeurIy unusubIe Ior un uLLenuuLed
vuccIne. OLIer sLruIns become Loo weuk us LIey ure cuILured repeuLedIy, und LIese
Loo ure unuccepLubIe Ior vuccIne use. Ike LIe porrIdge, cIuIr, und bed LIuL
GoIdIIocks IIked, onIy some vIruses ure "jusL rIgIL," reucIIng u IeveI oI uLLenuuLIon
LIuL mukes LIem uccepLubIe Ior vuccIne use, und noL cIungIng In sLrengLI. RecenL
moIecuIur LecInoIogy Ius mude possIbIe LIe uLLenuuLIon oI IIve vIrus by
moIecuIur munIpuIuLIon, buL LIIs meLIod Is sLIII rure.
O ; TIe vIrus Is LIen sepuruLed Irom LIe medIum In wIIcI IL Ius been grown.
VuccInes wIIcI ure oI severuI Lypes (us mosL ure) ure combIned beIore puckugIng.
TIe ucLuuI umounL oI vuccIne gIven Lo u puLIenL wIII be reIuLIveIy smuII compured
wILI LIe medIum In wIIcI IL Is gIven. DecIsIons ubouL wIeLIer Lo use wuLer,
uIcoIoI, or some oLIer soIuLIon Ior un InjecLubIe vuccIne, Ior exumpIe, ure mude
uILer repeuLed LesLs Ior suIeLy, sLerIIILy, und sLubIIILy.
"oulity Control
To proLecL boLI LIe purILy oI LIe vuccIne und LIe suIeLy oI LIe workers wIo muke und
puckuge LIe vuccIne, condILIons oI IuboruLory cIeunIIness ure observed LIrougIouL LIe
procedure. AII LrunsIers oI vIrus und medIu ure conducLed under sLerIIe condILIons, und
uII InsLrumenLs used ure sLerIIIzed In un uuLocIuve (u mucIIne LIuL kIIIs orgunIsms by
IeuL, und wIIcI muy be us smuII us u jeweI box or us Iurge us un elevutor) beIore und
uILer use. Workers perIormIng LIe procedures weur proLecLIve cIoLIIng wIIcI IncIudes
dIsposubIe Lyvek gowns, gIoves, booLIes, IuIr neLs, und Iuce musks. TIe munuIucLurIng
rooms LIemseIves ure specIuIIy uIr condILIoned so LIuL LIere Is u mInImuI number oI
purLIcIes In LIe uIr.
The Approvul Process
n order Ior prescrIpLIon drugs Lo be soId In LIe UnILed SLuLes, u drug munuIucLurer
musL meeL sLrIcL IIcensIng requIremenLs esLubIIsIed by Iuw und enIorced by LIe ood
und Drug AdmInIsLruLIon (DA).
AII prescrIpLIon drugs musL undergo LIree pIuses oI LesLIng, uILIougI duLu Irom LIe
second pIuse cun someLImes be used Lo meeL LIIrd pIuse requIremenLs. PIuse 1 LesLIng
musL prove LIuL u medIcIne Is suIe, or uL IeusL LIuL no unLowurd or unexpecLed eIIecLs
wIII occur Irom ILs udmInIsLruLIon. I u medIcIne pusses PIuse LesLIng, IL musL nexL be
LesLed Ior eIIIcucy-IL musL do wIuL IL Is supposed Lo do; medIcIne cunnoL be soId LIuL Is
useIess, or LIuL mukes cIuIms Ior un eIIecL LIuL IL does noL Iuve. InuIIy, PIuse LesLIng
Is desIgned Lo quunLIIy LIe eIIecLIveness oI u medIcIne or drug. AILIougI vuccInes ure
expecLed Lo Iuve eIIecLIveness cIose Lo 1oo%, cerLuIn medIcInes mIgIL weII be uccepLubIe
even II LIey Iuve IImILed eIIecLIveness, us Iong us LIe prescrIbIng pIysIcIun knows LIe
odds.
TIe enLIre munuIucLurIng process Is revIewed cureIuIIy by LIe DA wIIcI exumInes
records oI procedures us weII us vIsILIng LIe munuIucLurIng sILe ILseII. EucI sLep In LIe
munuIucLurIng process musL be documenLed, und LIe munuIucLurer musL demonsLruLe u
"sLuLe oI conLroI" Ior LIe munuIucLurIng process. TIIs meuns LIuL scrupuIous records
musL be kepL Ior every sLep In LIe process, und LIere musL be wrILLen InsLrucLIons Ior
eucI sLep oI LIe process. ExcepL In cuses oI grIevous error, LIe DA does noL deLermIne
II eucI sLep In u process Is correcL, buL onIy LIuL IL Is suIe und Is documenLed suIIIcIenLIy
Lo be perIormed us LIe munuIucLurer sLIpuIuLes.
The Iotore
ProducIng u usubIe, suIe unLIvIruI vuccIne InvoIves u Iurge number oI sLeps wIIcI,
unIorLunuLeIy, cunnoL uIwuys be done Ior eucI und every vIrus. TIere Is sLIII mucI Lo be
done und Ieurned. TIe new meLIods oI moIecuIur munIpuIuLIon Iuve cuused more LIun
one scIenLIsL Lo beIIeve LIuL LIe vuccIne LecInoIogy Is onIy now enLerIng u "goIden uge."
ReIInemenLs oI exIsLIng vuccInes ure possIbIe In LIe IuLure. RubIes vuccIne, Ior exumpIe,
produces sIde eIIecLs wIIcI muke LIe vuccIne unsuLIsIucLory Ior muss ImmunIzuLIon; In
LIe UnILed SLuLes, rubIes vuccIne Is now used onIy on puLIenLs wIo Iuve conLrucLed LIe
vIrus Irom un InIecLed unImuI und ure IIkeIy, wILIouL ImmunIzuLIon, Lo deveIop LIe IuLuI
dIseuse.
TIe HV vIrus, wIIcI bIoIogIsLs beIIeve cuuses ADS, Is noL currenLIy umenubIe Lo
LrudILIonuI vuccIne producLIon meLIods. TIe ADS vIrus rupIdIy muLuLes Irom one sLruIn
Lo unoLIer, und uny gIven sLruIn does noL seem Lo conIer ImmunILy uguInsL oLIer sLruIns.
AddILIonuIIy, u IImILed, ImmunIzIng eIIecL oI eILIer uLLenuuLed or kIIIed vIrus cunnoL be
demonsLruLed In eILIer LIe IuboruLory or In LesL unImuIs. No HV vuccIne Ius yeL been
deveIoped.
ooks
DuIbecco, RenuLo und HuroId S. GInsberg. Virolo. nd edILIon. J.B. IppIncoLL
Compuny, 1q88.
PIoLkIn, SLunIey A. und Edwurd A. MorLImer, Jr., eds. Vcccines. W.B. Suunders
Compuny, 1q88.