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TypesofVaccines
Scientiststakemanyapproachestodesigningvaccinesagainstamicrobe.Thesechoicesaretypicallybasedonfundamentalinformationaboutthemicrobe,suchashowit
infectscellsandhowtheimmunesystemrespondstoit,aswellaspracticalconsiderations,suchasregionsoftheworldwherethevaccinewouldbeused.Thefollowingare
someoftheoptionsthatresearchersmightpursue:
Live,attenuatedvaccines
Inactivatedvaccines
Subunitvaccines
Toxoidvaccines
Conjugatevaccines
DNAvaccines
Recombinantvectorvaccines

LIVE,ATTENUATEDVACCINES
Live,attenuatedvaccinescontainaversionofthelivingmicrobethathasbeenweakenedinthelabsoitcantcausedisease.Becausealive,attenuatedvaccineistheclosest
thingtoanaturalinfection,thesevaccinesaregoodteachersoftheimmunesystem:Theyelicitstrongcellularandantibodyresponsesandoftenconferlifelongimmunity
withonlyoneortwodoses.
Despitetheadvantagesoflive,attenuatedvaccines,therearesomedownsides.Itisthenatureoflivingthingstochange,ormutate,andtheorganismsusedinlive,
attenuatedvaccinesarenodifferent.Theremotepossibilityexiststhatanattenuatedmicrobeinthevaccinecouldreverttoavirulentformandcausedisease.Also,not
everyonecansafelyreceivelive,attenuatedvaccines.Fortheirownprotection,peoplewhohavedamagedorweakenedimmunesystemsbecausetheyveundergone
chemotherapyorhaveHIV,forexamplecannotbegivenlivevaccines.
Anotherlimitationisthatlive,attenuatedvaccinesusuallyneedtoberefrigeratedtostaypotent.Ifthevaccineneedstobeshippedoverseasandstoredbyhealthcareworkers
indevelopingcountriesthatlackwidespreadrefrigeration,alivevaccinemaynotbethebestchoice.
Live,attenuatedvaccinesarerelativelyeasytocreateforcertainviruses.Vaccinesagainstmeasles,mumps,andchickenpox,forexample,aremadebythismethod.Viruses
aresimplemicrobescontainingasmallnumberofgenes,andscientistscanthereforemorereadilycontroltheircharacteristics.Virusesoftenareattenuatedthroughamethod
ofgrowinggenerationsofthemincellsinwhichtheydonotreproduceverywell.Thishostileenvironmenttakesthefightoutofviruses:Astheyevolvetoadapttothenew
environment,theybecomeweakerwithrespecttotheirnaturalhost,humanbeings.
Live,attenuatedvaccinesaremoredifficulttocreateforbacteria.Bacteriahavethousandsofgenesandthusaremuchhardertocontrol.Scientistsworkingonalivevaccine
forabacterium,however,mightbeabletouserecombinantDNAtechnologytoremoveseveralkeygenes.Thisapproachhasbeenusedtocreateavaccineagainstthe
bacteriumthatcausescholera,Vibriocholerae,althoughthelivecholeravaccinehasnotbeenlicensedintheUnitedStates.

INACTIVATEDVACCINES
Scientistsproduceinactivatedvaccinesbykillingthediseasecausingmicrobewithchemicals,heat,orradiation.Suchvaccinesaremorestableandsaferthanlivevaccines:
Thedeadmicrobescantmutatebacktotheirdiseasecausingstate.Inactivatedvaccinesusuallydontrequirerefrigeration,andtheycanbeeasilystoredandtransportedin
afreezedriedform,whichmakesthemaccessibletopeopleindevelopingcountries.
Mostinactivatedvaccines,however,stimulateaweakerimmunesystemresponsethandolivevaccines.Soitwouldlikelytakeseveraladditionaldoses,orboostershots,to
maintainapersonsimmunity.Thiscouldbeadrawbackinareaswherepeopledonthaveregularaccesstohealthcareandcantgetboostershotsontime.

SUBUNITVACCINES
Insteadoftheentiremicrobe,subunitvaccinesincludeonlytheantigensthatbeststimulatetheimmunesystem.Insomecases,thesevaccinesuseepitopesthevery
specificpartsoftheantigenthatantibodiesorTcellsrecognizeandbindto.Becausesubunitvaccinescontainonlytheessentialantigensandnotalltheothermoleculesthat
makeupthemicrobe,thechancesofadversereactionstothevaccinearelower.
Subunitvaccinescancontainanywherefrom1to20ormoreantigens.Ofcourse,identifyingwhichantigensbeststimulatetheimmunesystemisatricky,timeconsuming
process.Oncescientistsdothat,however,theycanmakesubunitvaccinesinoneoftwoways:
Theycangrowthemicrobeinthelaboratoryandthenusechemicalstobreakitapartandgathertheimportantantigens.
TheycanmanufacturetheantigenmoleculesfromthemicrobeusingrecombinantDNAtechnology.Vaccinesproducedthiswayarecalledrecombinantsubunit
vaccines.
ArecombinantsubunitvaccinehasbeenmadeforthehepatitisBvirus.ScientistsinsertedhepatitisBgenesthatcodeforimportantantigensintocommonbakersyeast.The
yeastthenproducedtheantigens,whichthescientistscollectedandpurifiedforuseinthevaccine.Researchiscontinuingonarecombinantsubunitvaccineagainsthepatitis
Cvirus.

TOXOIDVACCINES
Forbacteriathatsecretetoxins,orharmfulchemicals,atoxoidvaccinemightbetheanswer.Thesevaccinesareusedwhenabacterialtoxinisthemaincauseofillness.
Scientistshavefoundthattheycaninactivatetoxinsbytreatingthemwithformalin,asolutionofformaldehydeandsterilizedwater.Suchdetoxifiedtoxins,calledtoxoids,are
safeforuseinvaccines.
Whentheimmunesystemreceivesavaccinecontainingaharmlesstoxoid,itlearnshowtofightoffthenaturaltoxin.Theimmunesystemproducesantibodiesthatlockonto
andblockthetoxin.Vaccinesagainstdiphtheriaandtetanusareexamplesoftoxoidvaccines.

CONJUGATEVACCINES
Ifabacteriumpossessesanoutercoatingofsugarmoleculescalledpolysaccharides,asmanyharmfulbacteriado,researchersmaytrymakingaconjugatevaccineforit.
Polysaccharidecoatingsdisguiseabacteriumsantigenssothattheimmatureimmunesystemsofinfantsandyoungerchildrencantrecognizeorrespondtothem.Conjugate
vaccines,aspecialtypeofsubunitvaccine,getaroundthisproblem.

Whenmakingaconjugatevaccine,scientistslinkantigensortoxoidsfromamicrobethataninfantsimmunesystemcanrecognizetothepolysaccharides.Thelinkagehelps
theimmatureimmunesystemreacttopolysaccharidecoatingsanddefendagainstthediseasecausingbacterium.
ThevaccinethatprotectsagainstHaemophilusinfluenzaetypeB(Hib)isaconjugatevaccine.

DNAVACCINES
ThumbnailofTheMakingofaDNAVaccineAgainstWestNileVirus
TheMakingofaDNAVaccineAgainstWestNileVirus.Viewtheillustration.
Credit:NIAID
Oncethegenesfromamicrobehavebeenanalyzed,scientistscouldattempttocreateaDNAvaccineagainstit.
Stillintheexperimentalstages,thesevaccinesshowgreatpromise,andseveraltypesarebeingtestedinhumans.DNAvaccinestakeimmunizationtoanewtechnological
level.Thesevaccinesdispensewithboththewholeorganismanditspartsandgetrightdowntotheessentials:themicrobesgeneticmaterial.Inparticular,DNAvaccines
usethegenesthatcodeforthoseallimportantantigens.
Researchershavefoundthatwhenthegenesforamicrobesantigensareintroducedintothebody,somecellswilltakeupthatDNA.TheDNAtheninstructsthosecellsto
maketheantigenmolecules.Thecellssecretetheantigensanddisplaythemontheirsurfaces.Inotherwords,thebodysowncellsbecomevaccinemakingfactories,
creatingtheantigensnecessarytostimulatetheimmunesystem.
ADNAvaccineagainstamicrobewouldevokeastrongantibodyresponsetothefreefloatingantigensecretedbycells,andthevaccinealsowouldstimulateastrongcellular
responseagainstthemicrobialantigensdisplayedoncellsurfaces.TheDNAvaccinecouldntcausethediseasebecauseitwouldntcontainthemicrobe,justcopiesofafew
ofitsgenes.Inaddition,DNAvaccinesarerelativelyeasyandinexpensivetodesignandproduce.
SocallednakedDNAvaccinesconsistofDNAthatisadministereddirectlyintothebody.Thesevaccinescanbeadministeredwithaneedleandsyringeorwithaneedleless
devicethatuseshighpressuregastoshootmicroscopicgoldparticlescoatedwithDNAdirectlyintocells.Sometimes,theDNAismixedwithmoleculesthatfacilitateits
uptakebythebodyscells.NakedDNAvaccinesbeingtestedinhumansincludethoseagainstthevirusesthatcauseinfluenzaandherpes.

RECOMBINANTVECTORVACCINES
RecombinantvectorvaccinesareexperimentalvaccinessimilartoDNAvaccines,buttheyuseanattenuatedvirusorbacteriumtointroducemicrobialDNAtocellsofthe
body.Vectorreferstothevirusorbacteriumusedasthecarrier.
Innature,viruseslatchontocellsandinjecttheirgeneticmaterialintothem.Inthelab,scientistshavetakenadvantageofthisprocess.Theyhavefiguredouthowtotakethe
roomygenomesofcertainharmlessorattenuatedvirusesandinsertportionsofthegeneticmaterialfromothermicrobesintothem.Thecarriervirusesthenferrythatmicrobial
DNAtocells.Recombinantvectorvaccinescloselymimicanaturalinfectionandthereforedoagoodjobofstimulatingtheimmunesystem.
Attenuatedbacteriaalsocanbeusedasvectors.Inthiscase,theinsertedgeneticmaterialcausesthebacteriatodisplaytheantigensofothermicrobesonitssurface.In
effect,theharmlessbacteriummimicsaharmfulmicrobe,provokinganimmuneresponse.
ResearchersareworkingonbothbacterialandviralbasedrecombinantvectorvaccinesforHIV,rabies,andmeasles.
Lastsyndicated:July23,2013
Thiscontentisbroughttoyouby:TheNationalInstituteofAllergyandInfectiousDiseases(NIAID)