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VACUNAS

FELIPEGARCÍAHOSPITALCLINIC.BARCELONA

RESUMENCROI2016

•  bNAbs•  Abstract32LBand311:infusiónVRC01usoterapéuLcoySTI•  Abstract90:VRC01usoprevenLvo•  Abstract303:bNAbsenPHI

•  VACUNASPREVENTIVAS–  Ensayosclínicos

•  Abstract318:reboostdeRV144RV305(Tailandia)•  VACUNASTERAPEUTICAS

–  Ensayosclínicos•  Abstract26LB:Vac4x-Romidepsina•  Abstract320:Vacunasqueredirigenrespuestasfrentearegionesconsv.

–  Patogenia:•  Abstract259LB:decómollegaralosfolículos•  Abstract22:CTLycART

–  entornoaSTI•  Abstract95LB:End-points•  Abstract346:End-points•  Abstract347:faltademarcadoressurrogadosderespuesta

RichardKoupCROI2016

ABSTRACT32LB

RichardKoupCROI2016

Abstract90

Abstract303:BroadlyReacLveNeutralizingAcLvityWithintheFirst6MonthsofHIV-1InfecLonTheseresultsindicatethattheinducConofbroadlyreacCvityneutralizingresponses,despitebeingrare,isfeasibleinrecentlyHIV-1infectedindividuals.ThisdatashouldencouragethesearchforimmunogensabletoelicitthiskindofresponsesinaprevenCveHIV-1vaccine. Abstract303




–  Ensayosclínicos•  Abstract26LB:Vac4x-Romidepsina•  Abstract320:Vacunasqueinducenrespuestasfrentearegionesconsv.



Abstract318

Conclusions:LateboostswithAIDSVAXB/E,withorwithoutALVAC-HIV,inducedplasmaHIV-specificIgGresponsesthatwerepredominantlyIgG1andIgG4,weresignificantlyhigherthanRV144responses,butdidnotimprovemagnitudenordurabilityofIgG3,andweresimilartosubtypesinCVM.ThesestudieshighlighttheneedfornewstrategiestodurablyboostHIV-specific,protecCveanCbodyresponsesobservedinRV144. Abstract318

ABSTRACT26LB

1. Host immune environment (inflammatory, Tregs) not able to generate of effective immunity

AntiPDL-1 abs: abstract 25 2. Expansion of pre-existing clones which are exhausted and target escape variants

Re-direct response towards vulnerable sites and away from irrelevant epitopes: abstract 320

3. No correct DC antigen presentation

4. B cell follicle sanctuary permits persistent productive virus infection

320ShapingCTLImmunodominanceWithConservedHIVVaccinesA`erEarlyTreatment(BCN01)Conclusions:HeterologousvaccinaConwithChAdV63andMVA.HIVconsvwasasafestrategytoinducenewandshiZpre-exisCngimmuneresponsetowardsconservedregionsofHIV-1inacohortofearly-treatedindividuals.Reservoirdecayduringfirstyearofearly-treatmentwasnotfurtherimpactedbyvaccinaCons.ThisisthefirsttherapeuCcvaccinetrialabletodemonstratearefocusingoftheCTLimmunodominancepa\erntowardsconservedregionsofHIV-1andmayprovidethebaseforeffecCvekickandkillstrategies.

Abstract320

1. Host immune environment (inflammatory, Tregs) not able to generate of effective immunity

AntiPDL-1 abs: abstract 25 2. Expansion of pre-existing clones which are exhausted and target escape variants

Re-direct response towards vulnerable sites and away from irrelevant epitopes: abstract 320

3. No correct DC antigen presentation Target DC, Intranodal injection

4. B cell follicle sanctuary permits persistent productive virus infection

Importancia de la IL-15 y CXCR5: abstract 259LB

•  LymphocyteexpansionanddifferenCaCon

•  EnhancedacCvaConandcytotoxicity

•  MigraConviaincreaseofCXCR5

259LBIncreasedEffectorCD8LymphocyteTraffickingtoLymphNodesInducedbyhetIL-15Abstract259LB

259LBIncreasedEffectorCD8LymphocyteTraffickingtoLymphNodesInducedbyhetIL-15Conclusions:WeexplorethepotenCalofIL-15asaviralreservoirreducingagentinART-treatedSIVinfectedmacaques.hetIL-15treatmentenhancesthenumber,acCvaConandcytotolyCcpotenCalofCD8cellsinLNandgerminalcenters,aknownsiteofviruspersistence.hetIL-15treatmentincombinaConwithpDNAvaccinetargeCngthe“Achilles’heel”ofthevirus,i.e.,thehighlyconservedregions(CE),invirussanctuaryareas(germinalcenters)isapromisingHIVeradicaConstrategy.

Abstract259LB

Abstract22

End-pointsSTI•  Virológicos

–  Set-pointviral(comomedia)–  Set-pointviral(proporciónpacientesbajounnivel)–  Deltadelset-pointviral(comomedia)–  Deltadelset-pointviral(proporciónpacientes0.5/1log)–  Picodecargaviral–  Areabajolacurva–  Tiempohastalaaparicióndelaviremia(MAP)–  Tiempohastaelpicodeviremia–  DoublingLme

•  Otros–  CD4–  ReiniciodecART

Abstract95LB

346RelaLonshipAmongViralLoadOutcomesinHIVTreatmentInterrupLonTrialsConclusions:OurresultsrevealacomplexrelaConshipbetweenseveralkeyvirologicfactorsinHIVATItrials,includingpre-ARTVL,viralreboundCming,andATIVLsetpoint.TheassociaConofdelayedviralreboundwithlowerATIVLsetpointsuggeststhepresenceofvirologicand/orimmunologicfactorsmediaCngbothoutcomes.

PercenLle Foldchange Log10Minimum 3.13*10-5 4.5

5% 0.02 1.69

25% 0.19 0.72

50% 0.50 0.3

68% 1.00 0

75% 1.85 -0.27

95% 11.87 -1.07

Maximum 148.72 -2.18

Abstract346

347ViralandImmuneCharacterisLcsofHIVPost-TreatmentControllersinACTGStudies•  Whilerare,PTCscanbeidenCfiedfromindividualswhowerenottreated

duringacuteHIVinfecCon.•  PTCsmaintainedasmallHIVreservoirevenaZerARTdisconCnuaCon

withoutasignificantincreaseinimmuneacCvaConorHIV-specificTorNKcellacCvity.

•  ThedetecConofpre-ATIHIVDNAandCA-RNAdidnotprecludethepossibilityofpost-treatmentcontrol,suggesCnginefficientviralreplicaConoranCviralimmuneacCvitymaymediatethiscontrol.

Abstract347

CONCLUSIONES•  bNAbsyvacunasprevenLvas:

1.   VRC01terapéuLconoevitaelrebote2.   VRC01secomienzaaestudiarcomoprevenLvo3.   bNAbssepuedenencontrarenPHI4.   ElboostconALVAC+gp120nosirve

•  VacunasterapéuLcas1.   Vac4x+romidepsinadisminuyeelreservoriodeforma

moderada,loquenosetraduceenuncambioenelreboteviralenelSTI

2.   SepuderedirigirlarespuestaCTLaregionesconservadasyestasCTLpuedenentrarensantuariosconIL-15

3.   LasCTLLenenunefectoadiLvoalcART4.   ElSTIesnecesarioyunend-pointvirológicomixtoeselque

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