vacunas y otras medidas preventivas...hiv-1 infected subjects treated with an autologous...
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VACUNAS Y OTRAS MEDIDAS VACUNAS Y OTRAS MEDIDAS PREVENTIVASPREVENTIVAS
FELIPE GARCFELIPE GARCÍÍAA
HOSPITAL CLINIC. BARCELONAHOSPITAL CLINIC. BARCELONA
RESUMEN 18TH CROIRESUMEN 18TH CROI
•• VACUNASVACUNAS
•• PRESERVATIVOPRESERVATIVO
•• CIRCUNCISIONCIRCUNCISION
•• PROFILAXIS PREEXPOSICION PROFILAXIS PREEXPOSICION ((PrePPreP)/MICROBICIDAS )/MICROBICIDAS
•• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)
•• TEST & TREATTEST & TREAT
•• VACUNASVACUNAS
•• PRESERVATIVOPRESERVATIVO
•• CIRCUNCISIONCIRCUNCISION
•• PROFILAXIS PREEXPOSICION PROFILAXIS PREEXPOSICION ((PrePPreP)/MICROBICIDAS )/MICROBICIDAS
•• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)
•• TEST & TREATTEST & TREAT
VACUNASVACUNAS
•• Anticuerpos neutralizantesAnticuerpos neutralizantes
•• PreclPreclíínicanica
•• Ensayos vacunas terapEnsayos vacunas terapééuticasuticas
•• Ensayos en vacunas preventivasEnsayos en vacunas preventivas
VACUNASVACUNAS
•• Anticuerpos neutralizantesAnticuerpos neutralizantes
•• Ensayos vacunas terapEnsayos vacunas terapééuticasuticas
•• Ensayos en vacunas preventivasEnsayos en vacunas preventivas
PaperPaper # 990# 990A Phase 1 A Phase 1 RandomizedRandomized ControlledControlled TrialTrial ofof a Triple a Triple AntiAnti --HIVHIV--1 Monoclonal 1 Monoclonal AntibodyAntibody Vaginal Vaginal MicrobicideMicrobicide C2F5, C4E10, C2F5, C4E10, andand C2G12C2G12
OA#140OA#140
PaperPaper # 339# 339RapidRapid SelectionSelection ofof HIVHIV--1 1 VirusesViruses withwith IncreasedIncreased AffinityAffinity
forfor thethe BroadlyBroadly NeutralizingNeutralizing AntibodyAntibody 4E10 4E10 UsingUsing a a RandomlyRandomly MutatedMutated EnvelopeEnvelope LibraryLibrary
•• a new approach to optimize the HIVa new approach to optimize the HIV --1 envelope protein 1 envelope protein ((envenv ) as ) as immunogenimmunogen : selection of variants with : selection of variants with increased affinity for broadly neutralizing antibod ies increased affinity for broadly neutralizing antibod ies from a library of from a library of virionsvirions with randomly mutated with randomly mutated envelope proteins. envelope proteins.
•• After 1 round of selection we succeeded in selectin g After 1 round of selection we succeeded in selectin g an envelope with a 5an envelope with a 5 --fold increase in affinity to 4E10 fold increase in affinity to 4E10 antibody. antibody.
VACUNASVACUNAS
•• Anticuerpos neutralizantesAnticuerpos neutralizantes
•• Ensayos vacunas terapEnsayos vacunas terapééuticasuticas
•• Ensayos en vacunas preventivasEnsayos en vacunas preventivas
PaperPaper # 384# 384IncreasedIncreased HIVHIV--specificspecific ImmunityImmunity in HIVin HIV --infectedinfected
IndividualsIndividuals VaccinatedVaccinated withwith a DNA Prime, a DNA Prime, rAd5rAd5 BoostBoostRegimenRegimen
•• a DNA a DNA plasmidplasmid prime, prime, rAd5rAd5 boostboost vaccinationvaccinationregimenregimen . .
•• 17 HIV17 HIV--infectedinfected menmen onon HAART HAART withwith <50 copies/<50 copies/ mLmLandand CD4+ T CD4+ T cellscells countscounts >350 >350 cellscells /mm3/mm3
•• receivedreceived 3 DNA 3 DNA plasmidplasmid primingpriming vaccinationsvaccinations , , eacheachseparatedseparated by 1 by 1 monthmonth . A . A rAd5rAd5 boostboost at 6 at 6 monthsmonths . .
•• TheThe vaccinevaccine regimenregimen usedused in in thisthis protocolprotocol isis safesafeandand immunogenicimmunogenic ; ;
•• vaccinationvaccination significantlysignificantly increasedincreased thethe frequencyfrequency ofofmeasurablemeasurable HIVHIV--specificspecific CTL. CTL.
•• TheThe CTL responses CTL responses inducedinduced werewere polyfunctionalpolyfunctional ..•• VaccinationVaccination diddid notnot decreasedecrease eithereither singlesingle --copycopy viral viral
loadsloads oror thethe frequencyfrequency ofof latentlatent virus, virus, •• diddid notnot induce induce newnew HIVHIV--specificspecific T T cellcell clones.clones.
PaperPaper # 387# 387StabilityStability ofof RestingResting CD4+ T CD4+ T CellCell HIVHIV--1 1 ReservoirsReservoirs followingfollowing ImmunizationImmunization withwithRecombinantRecombinant PoxvirusPoxvirus HIVHIV--1 1 VaccinesVaccines
HIV-1 infected subjects treated with an autologousdendritic cell therapy (AGS-004), exhibited a significant reduction in viral load (when compared to pre-ART viral load) and delay in the time to viral rebound during a 12
week structured treatment interruption (STI)
J.-P. Routy1, J. Angel2, S. Vezina3, C. Tremblay4, M. Loutfy5, J. Gill6,
J.-G. Baril7, F. Smaill8, R. G. Jain9, I. Y. Tcherepanova9, M.-R.
Boulassel10, T. Monesmith9, R. P. Sekaly11, C. A. Nicolette9, AGS 004-
001 Study Group1McGill University Health Centre, INSERM Unit 743, Montréal, Canada, 2Ottawa Hospital, Ottawa, Canada, 3Clinique Médicale l'Actuel,
Montréal, Canada, 4Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Canada, 5Maple Leaf Clinic, Toronto,
Canada, 6Southern Alberta Clinic, Calgary, Canada, 7Clinique Medicale du Quartier Latin, Montréal, Canada, 8Hamilton Health Sciences -
McMaster University Medical Centre, Hamilton, Canada, 9Argos Therapeutics Inc, Durham NC, United States, 10McGill University Health
Centre, Montréal, Canada, 11University of Montréal Research Centre, Montréal, Canada
Paper # 385
Manufacture of AGS-004AGS-004 is personalized for each subject and is prepared from dendritic cells (DCs) generated from autologous PBMCs (peripheral blood mononuclear cells) that have been collected by standard leukapheresis. The DCs are matured in culture in the presence of cytokines and then electroporated with CD40L RNA and autologous RNA amplified from the subject’s pre-ART plasma HIV sample (Routy and Nicolette, Immunotherapy, 2010 July, in press).
Figure 1. Overview of the preparation of AGS-004 via the ArcelisTM platform.
Study Design
Figure 2. Study Schema.
AGS-004 dosing every 4 weeks
8 weeks 12 weeks
ART 12 Week STI Booster Phase ART
AGS-004-001 is a single-arm, open-label, Phase 2 study of the safety and antiviral activity of AGS-004. Subjects receive 4 doses of AGS-004 while on ART and then interrupt antiretroviral drug treatment while receiving study drug.
Figure 5. Pre-ART vs. Week 12 of STI Log Change in Viral Load
PaperPaper # 386# 386LevelsLevels ofof CellularCellular ImmuneImmune ActivationActivation andand
MDSC Are MDSC Are ElevatedElevated afterafter AdministrationAdministration ofof ananHIVHIV--1 DC 1 DC TherapeuticTherapeutic VaccineVaccine
PaperPaper # 388# 388HIVHIV--1 1 TatTat EpitopeEpitope VaccineVaccine ImmunizationImmunization
SignificantlySignificantly Reduces Viral Load in ARTReduces Viral Load in ART --nanaïïveveAsymptomaticAsymptomatic HIVHIV--infectedinfected SubjectsSubjects
PaperPaper # 389# 389SafetySafety , , ReactogenicityReactogenicity , , andand ImmunogenicityImmunogenicity ofof
anan AdjuvantedAdjuvanted ProteinProtein HIV HIV VaccineVaccine in HIVin HIV --11--infectedinfected SubjectsSubjects
PaperPaper # 389# 389SafetySafety , , ReactogenicityReactogenicity , , andand ImmunogenicityImmunogenicity ofof
anan AdjuvantedAdjuvanted ProteinProtein HIV HIV VaccineVaccine in HIVin HIV --11--infectedinfected SubjectsSubjects
VACUNASVACUNAS
•• Anticuerpos neutralizantesAnticuerpos neutralizantes
•• Ensayos vacunas terapEnsayos vacunas terapééuticasuticas
•• Ensayos en vacunas preventivasEnsayos en vacunas preventivas
PaperPaper # 371# 371ImmunogenicityImmunogenicity ofof a a SubtypeSubtype C HIV C HIV VaccineVaccine RegimenRegimen , , thethe SAAVI SAAVI DNADNA--C2 C2 VaccineVaccine BoostedBoosted by SAAVI MVAby SAAVI MVA --C C VaccineVaccine : : ResultsResults ofof a a
Phase I Phase I StudyStudy ConductedConducted in in SouthSouth AfricaAfrica andand US US amongamong HIVHIV--uninfecteduninfected AdultsAdults (HVTN 073)(HVTN 073)
PaperPaper # 372# 372LongLong --termterm VaccineVaccine --inducedinduced HIV HIV SeropositivitySeropositivity amongamong HIVHIV--
uninfecteduninfected HealthyHealthy VolunteersVolunteers in ANRS COV1in ANRS COV1 --COHVAC COHVAC CohortCohort
PaperPaper # 373# 373SafetySafety andand ImmunogenicityImmunogenicity ofof a a ModifiedModified PoxPox VectorVector --basedbased VaccineVaccine CandidateCandidate ExpressingExpressing EnvEnv , Gag, , Gag, PolPol , ,
andand NefNef ProteinsProteins ofof HIVHIV--1 1 SubtypeSubtype B in HIVB in HIV --11–– HealthyHealthyVolunteersVolunteers : : ResultsResults ofof thethe RISVAC02 RISVAC02 TrialTrial
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Figure 2
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Figure 3A
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45.8%
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Figure 4A Figure 4B
•• VACUNASVACUNAS
•• PRESERVATIVOPRESERVATIVO
•• CIRCUNCISIONCIRCUNCISION
•• PROFILAXIS PREEXPOSICION PROFILAXIS PREEXPOSICION ((PrePPreP)/MICROBICIDAS )/MICROBICIDAS
•• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)
•• TEST & TREATTEST & TREAT
•• VACUNASVACUNAS
•• PRESERVATIVOPRESERVATIVO
•• CIRCUNCISIONCIRCUNCISION
•• PROFILAXIS PREEXPOSICION PROFILAXIS PREEXPOSICION ((PrePPreP)/MICROBICIDAS )/MICROBICIDAS
•• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)
•• TEST & TREATTEST & TREAT
•• VACUNASVACUNAS
•• PRESERVATIVOPRESERVATIVO
•• CIRCUNCISIONCIRCUNCISION
•• PROFILAXIS PREEXPOSICION PROFILAXIS PREEXPOSICION ((PrePPreP)/MICROBICIDAS)/MICROBICIDAS
•• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)
•• TEST & TREATTEST & TREAT
93
•• VACUNASVACUNAS
•• PRESERVATIVOPRESERVATIVO
•• CIRCUNCISIONCIRCUNCISION
•• PROFILAXIS PREEXPOSICION PROFILAXIS PREEXPOSICION ((PrePPreP)/MICROBICIDAS )/MICROBICIDAS
•• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)
•• TEST & TREATTEST & TREAT
•• VACUNASVACUNAS
•• PRESERVATIVOPRESERVATIVO
•• CIRCUNCISIONCIRCUNCISION
•• PROFILAXIS PREEXPOSICION PROFILAXIS PREEXPOSICION ((PrePPreP)/MICROBICIDAS )/MICROBICIDAS
•• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)
•• TEST & TREATTEST & TREAT
•• PaperPaper # 486# 486WhyWhy thethe MSMMSM--drivendriven HIV HIV EpidemicEpidemic IsIsNotNot SlowingSlowing DownDown Even in Even in thethePresencePresence ofof HAARTHAART