ADENOVIRUSASAVECTOR

INGENETHERAPYAND
VACCINES

http://www.virology.net/Big_Virology/EM/AdenoFD.jpg
 STRUCTURE
Size:7090nm

Nonenvelopedicosahedralvirus

Capsidcomprisedof3surfacecoat
proteins
Fibers
Pentons
Hexons
ReplicationCycle
1) AbsorptionandPenetration
Bindtocellsurfacereceptor
Enterscellbyendocytosis
2) Transcription
EarlytranscriptionCodesfornonstructural,regulatoryproteins
LatetranscriptionCodesforreplicationsubstratesandmachinery
3) Assembly
4) ExitCelllysis
Dontworry,adenovirusesarenot
transmittedthroughcontactwithpigs!

http://wwwdelivery.superstock.com/WI/223/1614/PreviewComp/SuperStock_1614R
2893.jpg
 NORMALVIRAL
TRANSMISSION

Airborne
&
Waterborne

TransmissionRoutes:DirectandIndirectContact
HandeyeContact

Fecal/OralContact

VenerealContact

RespiratoryDropletTransmittance

*Incubationperiodof29days
 www.stanford.edu/group/virus/adeno/2005/
ADENOVIRUSUSEINGENE
THERAPY
WHYADENOVIRUSESAREGOOD
VECTORSFORGENETHERAPY
INCANCERPATIENTS
Genetherapyworksbymanipulatingvirusesto
containgoodgenesinwhichtheycantransporttothe
cellstocodeforneededprotein/hormone/enzyme/etc
Theydonotincorporatetheirgenesintothehost
genome.
TheAdenovirusisubiquitousithasbeenisolatedfrom
alargenumberofdifferentspecieswithover100known
serotypes
Canrapidlyinfectalargerangeofhumancells

Lowpathogenicityinhumans

CanholdlargesegmentsofDNA

Genomedoesnotundergorearrangementathighrates

DNAiseasytomanipulatewithcurrentrecombinant
DNAtechniques
 Howthisvirusisusedin
cancertherapy
1) Mutagencompensation
Replacementorinactivationofoncogenes
2) Molecularchemotherapy(Suicide)
Alsoknownassuicideoftargettumorcells
3) Geneticimmunopotentiation
Modifiestumororimmunecellstoamplify
immunologicalrecognitionofneoplasticcells
4) Geneticmodulationofresistance/sensitivity
Modifysensitivityorresistanceofcellsto
chemotherapy(Chemoprotection)
5) Antiangiogenicgenetherapy(tumorsuppressor)
Targetsthedevelopmentofnewvesselsin
tumortissue,inhibitingitsgrowth
PERCENTAGEOFTHETYPESOF
GENETHERAPIESUSED
CancerTrialswith
AdenoviralVectors
ADENOVIRUSUSEASAVECTOR
INVACCINES
UsingaHumanAdenovirusVectorin
Vaccination
ADENOVIRUSVACCINEUSE
INHUMANS
HumanAdenovirusSerotypes
*Over100KnownSerotypes!
MostCommon:
HAvd4

HAvd7

Diagnosis
RespiratoryTractInfection
Commoncoldsymptoms
SoreThroat
Severecough
Swollenlymphnodes
Headache
Nonproductivecroupycough
Diagnosiscont.
IntestinalTractInfection
Abruptonsetofwaterdiarrhea
Fever
AbdominalTenderness
Vomiting

Notice:Bothcaseshaveverysimilarsymptoms
tocommoncoldandinfluenza

Respiratorysecretionculture
Stoolculture
Chestxray
Bloodwork
ADENOVIRUSVACCINEUSEIN
TRACHEOBRONCHITIS
KENNELCOUGH
CAv1:causesInfectiousCanine
Hepatitis
CAv2:causesInfectious
Tracheobronchitis
CanineDistemperAdenovirus
Type2MeaslesParainfluenza
VaccineisaModifiedLiveVaccine
VaccinationagainstCAdv2isdone
througha5wayor7wayvaccinein
whichotherinfectiousviralstrains
arevaccinatedagainst.
Administeredin2forms:
Intranasal&SubQ
FreezeDriedandstoredat27C
 FUTUREWORKUSING
ADENOVIRUSASAVECTOR
Themajorityofclinicaltrialsdoneusingthe
adenovirusingenetherapyhavebeenphase1
Phase1trialsareusedtodeterminesafety,
feasibility,andtoxicityoftheprocess
ThePhase1trialshavesetthestageforfuture
workwiththenextgenerationofAdenovectors
thatwillshowlessstimulationofthehostimmune
systemandcanbeselectivelytargetedtospecific
tissues.

Liverecombinantadenovirusvaccinearebeing
developed
Provideshopeforpractitionersinusinga
moreeconomicalvaccinethatprovidesa
longerlastingimmunity(Gray).
Ongoingresearchisaimedatdetermining
effectivenessofrecombinantvaccinesin
animals
REFERENCES
BaurschmitzG.J.,BarkerS.D.,HemminkiA.
AdenoviralGeneTherapyforCancerfromVectorstoTargetedand
ReplicationCompetentAgents.InternationalJournalofOncology.2002.

McCormickF.CancerGeneTherapy:FringeorCuttingEdge?2001.Nature
ReviewsCancer.1:1:2:pg130142.

VorburgerS.A.,HuntK.K.AdenoviralGeneTherapy.Oncologist.2002.7:46
59.

WagnerE.,HewlettM.J.,BloomD.C.,CameriniD.2008.BasicVirology.
BlackwellPublishing.,M.A.452pp.

AkusjrviG,PetterssonU,RobertsRJ:Structureandfunctionofthe
adenovirus2genome.InDoerflerW(ed):AdenovirusDNA.
MartinusNijhoff,Boston,1986.

Fields.Virology,3rdedition..LippincottRaven:Philadelphia,1996.
pp.21112171.

Gray,G.C.AdenovirusTransmissionWorthyofourAttention.JInfectDis.
194:871873,2006editorial.