VACUNAS FELIPE GARCÍA HOSPITAL CLINIC. BARCELONA RESUMEN 17TH CROI.
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Transcript of VACUNAS FELIPE GARCÍA HOSPITAL CLINIC. BARCELONA RESUMEN 17TH CROI.
VACUNASVACUNAS
FELIPE GARCÍAFELIPE GARCÍAHOSPITAL CLINIC. BARCELONAHOSPITAL CLINIC. BARCELONA
RESUMEN 17TH CROIRESUMEN 17TH CROI
• TEST & TREATTEST & TREAT• PROFILAXIS PREEXPOSICION (PreP)PROFILAXIS PREEXPOSICION (PreP)• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)• MICROBICIDASMICROBICIDAS• VACUNASVACUNAS
• TEST & TREATTEST & TREAT• PROFILAXIS PREEXPOSICION (PreP)PROFILAXIS PREEXPOSICION (PreP)• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)• MICROBICIDASMICROBICIDAS• VACUNASVACUNAS
TEST & TREATTEST & TREAT
33 33 Decreases in Community Viral Load Decreases in Community Viral Load Are Associated with a Reduction in Are Associated with a Reduction in New HIV Diagnoses in San FranciscoNew HIV Diagnoses in San Francisco
88LB 88LB an association between expanded HAART coverage, decreased an association between expanded HAART coverage, decreased “community plasma HIV-1-viral load”, and decreased new HIV diagnoses“community plasma HIV-1-viral load”, and decreased new HIV diagnoses
• TEST & TREATTEST & TREAT• PROFILAXIS PREEXPOSICION (PreP)PROFILAXIS PREEXPOSICION (PreP)• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)• MICROBICIDASMICROBICIDAS• VACUNASVACUNAS
PREPPREPAntirretrovirales Modelos animalesAntirretrovirales Modelos animales83 83 Efficacy of Intermittent Prophylaxis with Tenofovir and Emtricitabine against Rectal Efficacy of Intermittent Prophylaxis with Tenofovir and Emtricitabine against Rectal
SHIV Transmission in MacaquesSHIV Transmission in Macaques– Grupo I: 2 h y +26 h HR 4.1 Grupo II: -2 h y +24 horasGrupo I: 2 h y +26 h HR 4.1 Grupo II: -2 h y +24 horas HR 4HR 4– Grupo III: -22 h y +2 h HR 16.7 Grupo IV: -3 d y +2 h HR 15.4Grupo III: -22 h y +2 h HR 16.7 Grupo IV: -3 d y +2 h HR 15.4– Grupo V: -7 d y +2 h HR 9.3 Grupo VI: -3 d HR 0.5Grupo V: -7 d y +2 h HR 9.3 Grupo VI: -3 d HR 0.5
950 950 SHIV-specific T Cell Responses During Successful PrEP and Following Infection During SHIV-specific T Cell Responses During Successful PrEP and Following Infection During PrEPPrEP
-Robust SHIV-specific T cell responses following -Robust SHIV-specific T cell responses following
successful PrEP and repeated rectal SHIV exposures. successful PrEP and repeated rectal SHIV exposures.
-These T cell responses did not prevent infections-These T cell responses did not prevent infections
in all animals during subsequent virus exposuresin all animals during subsequent virus exposures
-Intermittent detection and changes in epitope -Intermittent detection and changes in epitope
specificity suggest that memory T cells were not specificity suggest that memory T cells were not
efficiently induced during repeated virus exposures. efficiently induced during repeated virus exposures.
This might explain the inability of the T-cells This might explain the inability of the T-cells
to completely protect from subsequent infection.to completely protect from subsequent infection.
PREPPREPHumanosHumanos85 85 MVC 300mg BID for 8 daysMVC 300mg BID for 8 days
PK1PK1 PK2PK2
BPBP SESE**
SE:BPSE:BP* * GMRGMR
RT*RT* RT:BRT:BPPRatioRatio
BPBP SESE SE:BSE:BP P GMR GMR
RT*RT* RT:BRT:BPPRatioRatio
CC12h12h
(ng/mL or (ng/mL or ng/g)ng/g)
2121(7 to (7 to 52)52)
2424 11 1,3701,370
6060 4949(23 to (23 to 102)102)
3838(19 to (19 to 75)75)
0.7 0.7 (0.5 (0.5 to 1)to 1)
44894489 9191
AUCAUC12h12h
(ng*hr/(ng*hr/mL or mL or ng*hr/g)ng*hr/g)
1,7661,766(527 (527 to to 3,199)3,199)
919133
0.60.6 14,3114,3188
99 1,9531,953(1,417 (1,417 to to 4,687)4,687)
11961196(655 (655 to to 2,577)2,577)
0.6 0.6 (0.5 (0.5 to to 0.8)0.8)
58,7458,7444
2828
MVC AUCs in semen: 56% (1 doses) and 62% (8 days) lower than BPMVC AUCs in semen: 56% (1 doses) and 62% (8 days) lower than BP
MVC AUC in RT: 9-fold (1 doses) and 28-fold (8 days) blood plasma. MVC AUC in RT: 9-fold (1 doses) and 28-fold (8 days) blood plasma.
• TEST & TREATTEST & TREAT• PROFILAXIS PREEXPOSICION (PreP)PROFILAXIS PREEXPOSICION (PreP)• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)• MICROBICIDASMICROBICIDAS• VACUNASVACUNAS
PEPPEP
• 956956 Open Randomized Multicenter Clinical Trial Open Randomized Multicenter Clinical Trial Comparing Zidovudine/Lamivudine (ZDV/3TC) plus Comparing Zidovudine/Lamivudine (ZDV/3TC) plus Lopinavir/r (LPV/r) or plus Atazanavir (ATV) Used as Lopinavir/r (LPV/r) or plus Atazanavir (ATV) Used as Postexposure Prophylaxis (PEP) for HIV InfectionPostexposure Prophylaxis (PEP) for HIV Infection
Adverse Events (AE)Adverse Events (AE) Lop/rLop/r AtzAtz pp
People with AE (% arm) People with AE (% arm) 50(49%)50(49%) 42(43%)42(43%) 0.30.3
Total AE (% of Total AE)Total AE (% of Total AE) 94(63%)94(63%) 56(37%)56(37%)
AE Gastrointestinal (% arm AE)AE Gastrointestinal (% arm AE) 66(70%)66(70%) 23(41%)23(41%) 0.00040.0004
AE Neuropsychiatric (% arm AE)AE Neuropsychiatric (% arm AE) 10(11%)10(11%) 9(16%)9(16%) 0.30.3
AE Hepatic (% arm AE)AE Hepatic (% arm AE) 1(1%)1(1%) 9(16%)9(16%) 0.00030.0003
AE Systemic (% arm AE)AE Systemic (% arm AE) 16(17%)16(17%) 13(23%)13(23%) 0.80.8
AE Dermatologic (% arm AE)AE Dermatologic (% arm AE) 1(1%)1(1%) 0(0%)0(0%) 0.40.4
AE ENT (% arm AE)AE ENT (% arm AE) 0(0%)0(0%) 2(4%)2(4%) 0.060.06
Discontinued study result AE (% arm)Discontinued study result AE (% arm) 7(7%)7(7%) 10(10%)10(10%) 0.40.4
Median period before discontinued result AE (days)Median period before discontinued result AE (days) 44 1212 0.230.23
Severity AE*Severity AE*
Grade I (% people with AE arm)Grade I (% people with AE arm) 43(86%)43(86%) 34(81%)34(81%) 0.50.5
Grade II (% people with AE arm)Grade II (% people with AE arm) 4(8%)4(8%) 7(17%)7(17%) 0.20.2
Grade III (% people with AE arm)Grade III (% people with AE arm) 3(6%)3(6%) 1(2%)1(2%) 0.40.4
Grade IV (% people with AE arm)Grade IV (% people with AE arm) 0(0%)0(0%) 0(0%)0(0%)
Withdrawal Lopinavir/r Arm
0
20
40
60
80
100
120
140
Starting PEP Baseline Week 4 Week 12 Week 24
131 (0%)
102 (22%)
74 (44%)
55 (58%)
31 (77%)
Nu
mb
er
of
Pa
tie
nts
(%
Wit
hd
rav
al)
Withdrawal Atazanavir Arm
0
20
40
60
80
100
120
140
Starting PEP Baseline Week 4 Week 12 Week 24
124 (0%)
98 (21%)
70 (44%)
52 (58%)
33 (73%)
N
um
be
r o
f P
ati
en
ts (
%W
ith
dra
va
l)
Withdrawal Interval
22%
22%
14%
19%
Withdrawal Interval
21%
23%
14%
15%
• TEST & TREATTEST & TREAT• PROFILAXIS PREEXPOSICION (PreP)PROFILAXIS PREEXPOSICION (PreP)• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)• MICROBICIDASMICROBICIDAS• VACUNASVACUNAS
MICROBICIDAS 87LB MICROBICIDAS 87LB PRO 2000PRO 2000• Objetivo:Objetivo: probar la eficacia en humanos en un ensayo probar la eficacia en humanos en un ensayo
Fase III de Fase III de PRO2000PRO2000 (afecta a la unión inicial y fase de fusión (afecta a la unión inicial y fase de fusión del VIH)del VIH)
• Resultados: Resultados: – Se randomizaron Se randomizaron 93859385 mujeres a 4 ramas: mujeres a 4 ramas: placebo vs PRO2000placebo vs PRO2000..
– Incidencia 4.7 (82/1741) and 3.9 (67/1717)/100 person-Incidencia 4.7 (82/1741) and 3.9 (67/1717)/100 person-years respectively; HR = 1.21, 95%CI 0.88 to 1.68years respectively; HR = 1.21, 95%CI 0.88 to 1.68
949949 Tenofovir Gel Protects Macaques Against SHIV Exposures Three Days after Vaginal Application
• TEST & TREATTEST & TREAT• PROFILAXIS PREEXPOSICION (PreP)PROFILAXIS PREEXPOSICION (PreP)• PROFILAXIS POSTEXPOSICION (PEP)PROFILAXIS POSTEXPOSICION (PEP)• MICROBICIDASMICROBICIDAS• VACUNASVACUNAS
VACUNA FRENTE A VIHVACUNA FRENTE A VIH
• VACUNA TERAPEUTICAVACUNA TERAPEUTICA
• VACUNA PREVENTIVAVACUNA PREVENTIVA
VACUNASVACUNAS
• HUMANOSHUMANOS– Ensayos vacunas terapéuticasEnsayos vacunas terapéuticas
• 76 76 Factors Associated with Viral Rebound in HIV-Positive Subjects Receiving a Factors Associated with Viral Rebound in HIV-Positive Subjects Receiving a Therapeutic HIV-1 gag VaccineTherapeutic HIV-1 gag Vaccine
• 77 77 A Phase I Double-blind Placebo-controlled Randomized Study of a Therapeutic A Phase I Double-blind Placebo-controlled Randomized Study of a Therapeutic Vaccine Using Autologous DC Loaded with Autologous HIV-1 in Untreated Vaccine Using Autologous DC Loaded with Autologous HIV-1 in Untreated Patients with Asymptomatic Chronic HIV InfectionPatients with Asymptomatic Chronic HIV Infection
• 385 385 Increased HIV-specific Immunity in HIV-infected Individuals Vaccinated with Increased HIV-specific Immunity in HIV-infected Individuals Vaccinated with a DNA Prime, rAd5 Boost Regimena DNA Prime, rAd5 Boost Regimen
– Ensayos en vacunas preventivasEnsayos en vacunas preventivas• 74 74 RV 144 Update: Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 RV 144 Update: Vaccination with ALVAC and AIDSVAX to Prevent HIV-1
Infection in Thai AdultsInfection in Thai Adults
• 75 75 Vaccine-induced Changes in Breakthrough HIV-1 Sequences from the Step Vaccine-induced Changes in Breakthrough HIV-1 Sequences from the Step TrialTrial
• 78LB 78LB Optimal Priming of Poxvirus Vector-based HIV Vaccine Regimens Requires Optimal Priming of Poxvirus Vector-based HIV Vaccine Regimens Requires 3 DNA Injections: Results of the Randomized Multicentre EV03/ANRS Vac20 3 DNA Injections: Results of the Randomized Multicentre EV03/ANRS Vac20 Phase I/II TrialPhase I/II Trial
VACUNASVACUNAS• MODELOS ANIMALESMODELOS ANIMALES
– AdyuvantesAdyuvantes• 79LB 79LB Preclinical Studies on DNA/MVA Vaccines: Co-expressed GM-CSF, a Strong Adjuvant for Preclinical Studies on DNA/MVA Vaccines: Co-expressed GM-CSF, a Strong Adjuvant for
Prevention of InfectionPrevention of Infection
• 381 381 Modulation of Vaccine Responses by RANTES Significantly Lowers Viral Replication following Modulation of Vaccine Responses by RANTES Significantly Lowers Viral Replication following SIVmac251 ChallengeSIVmac251 Challenge
• 382 382 IL-28B Adjuvant Increases Granzyme B Content and CD107a Expression in HIV-specific CD8+ T Cells IL-28B Adjuvant Increases Granzyme B Content and CD107a Expression in HIV-specific CD8+ T Cells after DNA Vaccinationafter DNA Vaccination
– VectoresVectores• 81 81 Lentiviral Vector-based Anti-HIV-1 Vaccine Induces Strong T Cell and Antibody Responses in Lentiviral Vector-based Anti-HIV-1 Vaccine Induces Strong T Cell and Antibody Responses in
Macaques, with and without DNA PrimingMacaques, with and without DNA Priming
– Activación y Marcadores surrogadosActivación y Marcadores surrogados• 378 378 Control of Immune Activation prior to SIV Challenge Is Tightly Linked to the Protective CD8+ T Cell Control of Immune Activation prior to SIV Challenge Is Tightly Linked to the Protective CD8+ T Cell
Immunity Induced by a Live, Attenuated AIDS VaccineImmunity Induced by a Live, Attenuated AIDS Vaccine
• 384 384 MVA-SIV Boosting of AdHu5-SIV Immunized Rhesus Macaques Induces Higher Levels of SIV-specific MVA-SIV Boosting of AdHu5-SIV Immunized Rhesus Macaques Induces Higher Levels of SIV-specific CD8+ T Cells but Results in Increased Virus Replication after SIVmac239 ChallengeCD8+ T Cells but Results in Increased Virus Replication after SIVmac239 Challenge
• ESTUDIOS NEUTRALIZACIONESTUDIOS NEUTRALIZACION• 361 361 Identification of Sera with Broad and Potent Cross-Neutralizing Activity against HIV-1 in a Group of Identification of Sera with Broad and Potent Cross-Neutralizing Activity against HIV-1 in a Group of
Patients with Undetectable Viral LoadsPatients with Undetectable Viral Loads
• 82 82 Broad HIV Neutralizing Antibodies Can Be Elicited by the GBV-C glycoprotein E2 and Neutralize HIV Broad HIV Neutralizing Antibodies Can Be Elicited by the GBV-C glycoprotein E2 and Neutralize HIV via a 2F5-like Mechanismvia a 2F5-like Mechanism
DC-SIGN
VIH
CÉLULAS DENDRÍTICAS E INFECCIÓN POR EL VIH
- Facilitan la infección por el VIHI.P.
VACUNASVACUNASEnsayos vacunas terapéuticas Ensayos vacunas terapéuticas 77 77 Vacuna de CDVacuna de CD
0 4 8 12 16 20 24 28 32 36 40 44 48-0.4
-0.2
0.0
0.2
0.4
DC-PLACEBODC-HIV-1
DC-PLACEBO 12 12 12 12 11 11 11 9DC-HIV-1 10 10 10 10 8 8 8 7
0.08
0.03
0.04
AUC,P= 0.06
WEEKS
L
og
10 P
VL
(co
pie
s/m
l)
DC-PLACEBO
-0.1 0.0 0.1 0.2 0.3 0.4-1500
-1000
-500
0
500
1000
r= 0,53, p=0.13
log10 plasma viral load (copies/ml)
S
FC
/106 P
BM
C
DC-HIV-1
-0.4 -0.2 0.0 0.2-2000
-1000
0
1000
2000r= -0.54, p=0.10
log10 plasma viral load (copies/ml)
S
FC
/106 P
BM
C
0 4 8 12 16 20 24 28 32 36 40 44 48-1500
-1000
-500
0
500
1000
1500
-0.4
-0.2
0.0
0.2
0.4
CTLPVL
DC-PLACEBO
PLACEBO 12 11 12 12 11 11 11 9
WEEKS
S
FC
/106 P
BM
C
L
og
10 P
VL
(co
pie
s/m
l)
0 4 8 12 16 20 24 28 32 36 40 44 48-1500
-1000
-500
0
500
1000
1500
-0.4
-0.2
0.0
0.2
0.4
CTL
PVL
DC-HIV
VACCINE 10 10 10 10 7 8 8 7
WEEKS
S
FC
/106 P
BM
C
L
og
10 P
VL
(co
pie
s/m
l)
A modest decrease in VL was observed in vaccine recipients and was correlated A modest decrease in VL was observed in vaccine recipients and was correlated with a moderate increase of HIV specific T cell responses.with a moderate increase of HIV specific T cell responses.
VACUNASVACUNAS
76 76 factors independently associated with lower ATI VL: factors independently associated with lower ATI VL:
included lower pre-antiretroviral therapy VL, included lower pre-antiretroviral therapy VL,
decreased proportion of HLA-associated escape decreased proportion of HLA-associated escape
mutations in Gag, mutations in Gag,
absence of unfavorable HLA class I alleles, absence of unfavorable HLA class I alleles,
vaccine arm.vaccine arm.
Ensayos vacunas terapéuticasEnsayos vacunas terapéuticas
385 385 Increased HIV-specific Immunity in HIV-infected Increased HIV-specific Immunity in HIV-infected Individuals Vaccinated with a DNA Prime, rAd5 Boost Individuals Vaccinated with a DNA Prime, rAd5 Boost RegimenRegimen
VACUNASVACUNAS
Ensayos en vacunas preventivasEnsayos en vacunas preventivas74 74 RV 144 Update: Vaccination with ALVAC RV 144 Update: Vaccination with ALVAC
and AIDSVAX to Prevent HIV-1 Infection and AIDSVAX to Prevent HIV-1 Infection
in Thai Adultsin Thai Adults
75 75 breakthrough viruses from vaccinees breakthrough viruses from vaccinees diverged further from the Step vaccine diverged further from the Step vaccine sequence than viruses from placebo sequence than viruses from placebo recipients at potentially immune reactive recipients at potentially immune reactive sitessites
78LB 78LB Optimal Priming of Poxvirus Vector-based HIV Vaccine Regimens Optimal Priming of Poxvirus Vector-based HIV Vaccine Regimens Requires 3 DNA Injections: Results of the Randomized Multicentre Requires 3 DNA Injections: Results of the Randomized Multicentre EV03/ANRS Vac20 Phase I/II TrialEV03/ANRS Vac20 Phase I/II Trial
VACUNASVACUNAS
MODELOS ANIMALESMODELOS ANIMALESAdyuvantesAdyuvantes
79LB 79LB DNA/MVA Vaccines DNA/MVA Vaccines
+ GM-CSF (NA)+ GM-CSF (NA)
CONTROLSCONTROLS DNA/MVADNA/MVA DNA/MVA + DNA/MVA + GM-CSFGM-CSF
INFECTIONSINFECTIONS 9/99/9 6/86/8 2/72/7
381 381 DNA+ IL12 or DNA+RANTES DNA+ IL12 or DNA+RANTES can modulate immune can modulate immune responses and significantly responses and significantly impact viral replication following impact viral replication following viral challenge. viral challenge. - the magnitude, proliferative - the magnitude, proliferative capacity, or polyfunctionality of capacity, or polyfunctionality of the responses does not predict the responses does not predict the outcome of viral challengethe outcome of viral challenge
382 382 Plasmid HIV gag/pol + Plasmid HIV gag/pol + IL-28BIL-28B
VACUNASVACUNASMODELOS ANIMALESMODELOS ANIMALES
VectoresVectores
81 81 Lentiviral Vector-based Anti-HIV-1 Vaccine Induces Strong T Cell and Antibody Lentiviral Vector-based Anti-HIV-1 Vaccine Induces Strong T Cell and Antibody Responses in Macaques, with and without DNA PrimingResponses in Macaques, with and without DNA Priming
Activación y Marcadores surrogadosActivación y Marcadores surrogados
378 378 Control of Immune Activation prior to SIV Challenge Is Tightly Linked to the Protective Control of Immune Activation prior to SIV Challenge Is Tightly Linked to the Protective CD8+ T Cell Immunity Induced by a Live, Attenuated AIDS VaccineCD8+ T Cell Immunity Induced by a Live, Attenuated AIDS Vaccine
384 384 MVA-SIV Boosting of AdHu5-SIV Immunized Rhesus Macaques Induces Higher Levels MVA-SIV Boosting of AdHu5-SIV Immunized Rhesus Macaques Induces Higher Levels of SIV-specific CD8+ T Cells but Results in Increased Virus Replication after of SIV-specific CD8+ T Cells but Results in Increased Virus Replication after SIVmac239 ChallengeSIVmac239 Challenge
VACUNASVACUNAS• ESTUDIOS NEUTRALIZACIONESTUDIOS NEUTRALIZACION
• 361 361 Identification of Sera with Broad and Potent Cross-Neutralizing Activity against HIV-1 in a Identification of Sera with Broad and Potent Cross-Neutralizing Activity against HIV-1 in a Group of Patients with Undetectable Viral LoadsGroup of Patients with Undetectable Viral Loads
• 82 82 GB virus C AGB virus C Anti-E2 antibodies neutralize HIV-1 and 2, as well as SIV by targeting nti-E2 antibodies neutralize HIV-1 and 2, as well as SIV by targeting Phospholipids within the retroviral lipid bilayer via a 2F5-like MechanismPhospholipids within the retroviral lipid bilayer via a 2F5-like Mechanism
Number of viruses
neutralized a
Detectable viral loads
ID90<1/20
0
ID90<1/200
0
0 109 202
1 78 3
2 15 0
3 1 1
4 2 0
5 0 0
6 1 0
Number of viruses
neutralized a
Undetectable viral loads
ID90<1/20
0
ID90<1/200
0
0 109 188
1 28 19
2 1 8
3 1 1
4 0 3
5 1 2
6 92 10
RESUMEN RESUMEN • TEST & TREATTEST & TREAT
– Tratamiento generalizado se asocia con disminución de la incidenciaTratamiento generalizado se asocia con disminución de la incidencia
• PROFILAXIS PREEXPOSICION (PreP)PROFILAXIS PREEXPOSICION (PreP)– iPreP con Truvada disminuye la infección siempre que se asocie con iPreP con Truvada disminuye la infección siempre que se asocie con
refuerzo post.refuerzo post.– La exp repetida aumenta las respuestas específicas, pero no son eficacesLa exp repetida aumenta las respuestas específicas, pero no son eficaces– MVC con una dosis tiene niveles altos en mucosa rectalMVC con una dosis tiene niveles altos en mucosa rectal
• PROFILAXIS POSTEXPOSICION (PEP): PROFILAXIS POSTEXPOSICION (PEP): – La tasa de abandonos es muy alta, no existen diferencias en efectos La tasa de abandonos es muy alta, no existen diferencias en efectos
adversos Atazanavir vs Lopinavir/r adversos Atazanavir vs Lopinavir/r
• MICROBICIDAS: MICROBICIDAS: – PRO 2000 no funcionaPRO 2000 no funciona
RESUMEN VACUNASRESUMEN VACUNAS
• HUMANOSHUMANOS– Ensayos vacunas terapéuticasEnsayos vacunas terapéuticas
• La vacuna de CD en pacientes sin tto disminuyó 0.5 log la CV La vacuna de CD en pacientes sin tto disminuyó 0.5 log la CV asociado con respuestas específicasasociado con respuestas específicas
• DNA + Ad5 induce respuestas en pacientes infectados por VIHDNA + Ad5 induce respuestas en pacientes infectados por VIH
• Un HLA favorable puede influir la respuesta a las vacunasUn HLA favorable puede influir la respuesta a las vacunas
– Ensayos en vacunas preventivasEnsayos en vacunas preventivas• En el STEP las respuestas inducidas podrían haber protegido En el STEP las respuestas inducidas podrían haber protegido
frente a los virus provocando un escapefrente a los virus provocando un escape
• Los ensayos en fase I son necesarios para probar diversas Los ensayos en fase I son necesarios para probar diversas estrategias como 3 dosis de DNA + 1 NYVAC es superior a 2/2estrategias como 3 dosis de DNA + 1 NYVAC es superior a 2/2
RESUMEN VACUNASRESUMEN VACUNAS• MODELOS ANIMALESMODELOS ANIMALES
– Adyuvantes: Adyuvantes: adyuvantes del tipo de GM-CSF, RANTES o IL-28 utilizados adyuvantes del tipo de GM-CSF, RANTES o IL-28 utilizados dentro de la propia vacuna pueden mejorar la respuesta virológica e dentro de la propia vacuna pueden mejorar la respuesta virológica e inmunológicainmunológica
– Vectores: Vectores: los vectores lentivirales son prometedoreslos vectores lentivirales son prometedores
– Activación y Marcadores surrogados: Activación y Marcadores surrogados: la presencia de respuesta específica no la presencia de respuesta específica no se relaciona con el control de la replicación viral, este control parece depender se relaciona con el control de la replicación viral, este control parece depender de la capacidad de las vacunas de inducir respuestas CD8 y disminuir de la capacidad de las vacunas de inducir respuestas CD8 y disminuir activación en mucosasactivación en mucosas
• ESTUDIOS NEUTRALIZACIONESTUDIOS NEUTRALIZACION– Los pacientes en tratamiento presentan una mejor respuesta neutralizanteLos pacientes en tratamiento presentan una mejor respuesta neutralizante
– Ac frente a Hep GB son neutralizantes de forma parecida a otros aislados de Ac frente a Hep GB son neutralizantes de forma parecida a otros aislados de pacientes infectados por VIH pacientes infectados por VIH