VACUNAS FELIPE GARCÍA HOSPITAL CLINIC. BARCELONA RESUMEN CROI 2016
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1 VACUNAS FELIPE GARCÍA HOSPITAL CLINIC. BARCELONA RESUMEN CROI 2016
2 bnabs Abstract 32LB and 311: infusión VRC01 uso terapéulco y STI Abstract 90: VRC01 uso prevenlvo Abstract 303: bnabs en PHI VACUNAS PREVENTIVAS Ensayos clínicos Abstract 318: reboost de RV144 RV 305 (Tailandia) VACUNAS TERAPEUTICAS Ensayos clínicos Abstract 26LB: Vac4x-Romidepsina Abstract 320: Vacunas que redirigen respuestas frente a regiones consv. Patogenia: Abstract 259LB: de cómo llegar a los folículos Abstract 22: CTL y cart en torno a STI Abstract 95LB: End-points Abstract 346: End-points Abstract 347: falta de marcadores surrogados de respuesta
3 bnabs Abstract 32LB and 311: infusión VRC01 uso terapéulco y STI Abstract 90: VRC01 uso prevenlvo Abstract 303: bnabs en PHI VACUNAS PREVENTIVAS Ensayos clínicos Abstract 318: reboost de RV144 RV 305 (Tailandia) VACUNAS TERAPEUTICAS Ensayos clínicos Abstract 26LB: Vac4x-Romidepsina Abstract 320: Vacunas que redirigen respuestas frente a regiones consv. Patogenia: Abstract 259LB: de cómo llegar a los folículos Abstract 22: CTL y cart en torno a STI Abstract 95LB: End-points Abstract 346: End-points Abstract 347: falta de marcadores surrogados de respuesta
4 Richard Koup CROI 2016
5 Richard Koup CROI 2016
6 Richard Koup CROI 2016
7 ABSTRACT 32LB
8 ABSTRACT 32LB
9 ABSTRACT 32LB
10 ABSTRACT 32LB
11 Richard Koup CROI 2016
12 Abstract 90
13 Abstract 90
14 Abstract 303: Broadly ReacLve Neutralizing AcLvity Within the First 6 Months of HIV-1 InfecLon These results indicate that the induccon of broadly reaccvity neutralizing responses, despite being rare, is feasible in recently HIV-1 infected individuals. This data should encourage the search for immunogens able to elicit this kind of responses in a prevencve HIV-1 vaccine. Abstract 303
15 bnabs Abstract 32LB and 311: infusión VRC01 uso terapéulco y STI Abstract 90: VRC01 uso prevenlvo Abstract 303: bnabs en PHI VACUNAS PREVENTIVAS Ensayos clínicos Abstract 318: reboost de RV144 RV 305 (Tailandia) VACUNAS TERAPEUTICAS Ensayos clínicos Abstract 26LB: Vac4x-Romidepsina Abstract 320: Vacunas que inducen respuestas frente a regiones consv. Patogenia: Abstract 259LB: de cómo llegar a los folículos Abstract 22: CTL y cart en torno a STI Abstract 95LB: End-points Abstract 346: End-points Abstract 347: falta de marcadores surrogados de respuesta
16 Abstract 318
17 Conclusions: Late boosts with AIDSVAX B/E, with or without ALVAC-HIV, induced plasma HIV-specific IgG responses that were predominantly IgG1 and IgG4, were significantly higher than RV144 responses, but did not improve magnitude nor durability of IgG3, and were similar to subtypes in CVM. These studies highlight the need for new strategies to durably boost HIV-specific, proteccve ancbody responses observed in RV144. Abstract 318
18 bnabs Abstract 32LB and 311: infusión VRC01 uso terapéulco y STI Abstract 90: VRC01 uso prevenlvo Abstract 303: bnabs en PHI VACUNAS PREVENTIVAS Ensayos clínicos Abstract 318: reboost de RV144 RV 305 (Tailandia) VACUNAS TERAPEUTICAS Ensayos clínicos Abstract 26LB: Vac4x-Romidepsina Abstract 320: Vacunas que redirigen respuestas frente a regiones consv. Patogenia: Abstract 259LB: de cómo llegar a los folículos Abstract 22: CTL y cart en torno a STI Abstract 95LB: End-points Abstract 346: End-points Abstract 347: falta de marcadores surrogados de respuesta
19 ABSTRACT 26LB
20 ABSTRACT 26LB
21 ABSTRACT 26LB
22 ABSTRACT 26LB
23 ABSTRACT 26LB
24 ABSTRACT 26LB
25 ABSTRACT 26LB
26 1. Host immune environment (inflammatory, Tregs) not able to generate of effective immunity AntiPDL-1 abs: abstract Expansion of pre-existing clones which are exhausted and target escape variants Re-direct response towards vulnerable sites and away from irrelevant epitopes: abstract No correct DC antigen presentation 4. B cell follicle sanctuary permits persistent productive virus infection
27 Abstract Shaping CTL Immunodominance With Conserved HIV Vaccines A`er Early Treatment (BCN01) Conclusions: Heterologous vaccinacon with ChAdV63 and MVA.HIVconsv was a safe strategy to induce new and shiz pre-exiscng immune response towards conserved regions of HIV-1 in a cohort of early-treated individuals. Reservoir decay during first year of early-treatment was not further impacted by vaccinacons. This is the first therapeucc vaccine trial able to demonstrate a refocusing of the CTL immunodominance pa\ern towards conserved regions of HIV-1 and may provide the base for effeccve kick and kill strategies.
28 1. Host immune environment (inflammatory, Tregs) not able to generate of effective immunity AntiPDL-1 abs: abstract Expansion of pre-existing clones which are exhausted and target escape variants Re-direct response towards vulnerable sites and away from irrelevant epitopes: abstract 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
29
30 Lymphocyte expansion and differencacon Enhanced accvacon and cytotoxicity MigraCon via increase of CXCR5 259LB Increased Effector CD8 Lymphocyte Trafficking to Lymph Nodes Induced by hetil-15 Abstract 259LB
31 Abstract 259LB 259LB Increased Effector CD8 Lymphocyte Trafficking to Lymph Nodes Induced by hetil-15 Conclusions: We explore the potencal of IL-15 as a viral reservoir reducing agent in ART-treated SIV infected macaques. hetil-15 treatment enhances the number, accvacon and cytotolycc potencal of CD8 cells in LN and germinal centers, a known site of virus persistence. hetil-15 treatment in combinacon with pdna vaccine targecng the Achilles heel of the virus, i.e., the highly conserved regions (CE), in virus sanctuary areas (germinal centers) is a promising HIV eradicacon strategy.
32 Abstract 22
33 Abstract 22
34 Abstract 22
35 Abstract 22
36 bnabs Abstract 32LB and 311: infusión VRC01 uso terapéulco y STI Abstract 90: VRC01 uso prevenlvo Abstract 303: bnabs en PHI VACUNAS PREVENTIVAS Ensayos clínicos Abstract 318: reboost de RV144 RV 305 (Tailandia) VACUNAS TERAPEUTICAS Ensayos clínicos Abstract 26LB: Vac4x-Romidepsina Abstract 320: Vacunas que redirigen respuestas frente a regiones consv. Patogenia: Abstract 259LB: de cómo llegar a los folículos Abstract 22: CTL y cart en torno a STI Abstract 95LB: End-points Abstract 346: End-points Abstract 347: falta de marcadores surrogados de respuesta
37 End-points STI Virológicos Set-point viral (como media) Set-point viral (proporción pacientes bajo un nivel) Delta del set-point viral (como media) Delta del set-point viral (proporción pacientes 0.5/1 log) Pico de carga viral Area bajo la curva Tiempo hasta la aparición de la viremia (MAP) Tiempo hasta el pico de viremia Doubling Lme Otros CD4 Reinicio de cart
38 End-points STI Virológicos Set-point viral (como media) Set-point viral (proporción pacientes bajo un nivel) Delta del set-point viral (como media) Delta del set-point viral (proporción pacientes 0.5/1 log) Pico de carga viral Area bajo la curva Tiempo hasta la aparición de la viremia (MAP) Tiempo hasta el pico de viremia Doubling Lme Otros CD4 Reinicio de cart
39
40 Abstract 95LB
41 Abstract 95LB
42 Abstract 346 PercenLle Fold change Log 10 Minimum 3.13* % % % % % % Maximum RelaLonship Among Viral Load Outcomes in HIV Treatment InterrupLon Trials Conclusions: Our results reveal a complex relaconship between several key virologic factors in HIV ATI trials, including pre-art VL, viral rebound Cming, and ATI VL set point. The associacon of delayed viral rebound with lower ATI VL set point suggests the presence of virologic and/or immunologic factors mediacng both outcomes.
43 347 Viral and Immune CharacterisLcs of HIV Post-Treatment Controllers in ACTG Studies While rare, PTCs can be idencfied from individuals who were not treated during acute HIV infeccon. PTCs maintained a small HIV reservoir even azer ART disconcnuacon without a significant increase in immune accvacon or HIV-specific T or NK cell accvity. The deteccon of pre-ati HIV DNA and CA-RNA did not preclude the possibility of post-treatment control, suggescng inefficient viral replicacon or ancviral immune accvity may mediate this control. Abstract 347
44 CONCLUSIONES bnabs y vacunas prevenlvas: 1. VRC01 terapéulco no evita el rebote 2. VRC01 se comienza a estudiar como prevenlvo 3. bnabs se pueden encontrar en PHI 4. El boost con ALVAC + gp120 no sirve Vacunas terapéulcas 1. Vac4x + romidepsina disminuye el reservorio de forma moderada, lo que no se traduce en un cambio en el rebote viral en el STI 2. Se pude redirigir la respuesta CTL a regiones conservadas y estas CTL pueden entrar en santuarios con IL Las CTL Lenen un efecto adilvo al cart 4. El STI es necesario y un end-point virológico mixto es el que proporciona más información
45 GRACIAS
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