Resumen IV: VACUNAS

Beatriz Mothe Pujadas, MD, PhD

Unidad VIH / Servicio Enf Infecciosas

Instituto Investigación Sida IrsiCaixa

Hospital Germans Trias i Pujol, Badalona

Resumen IV: VACUNAS

-NINGUNA plenaria, sesión de abstracts orales, discusión temática ni

simposio específico de vacunas terapéuticas!!!

-Sesiones de Pósters:

-P-C5: Vaccine Design and Testing

Resumen IV: VACUNAS

Temas relacionados seleccionados:

INFECCIÓN AGUDA – RESPUESTA CD8 – KICK & KILL – RhCMV/SIV

Pre-conference sessions (Sunday):

Advances in Immunology. Alexandra Trkola

Advances in HIV Cure. Huldrych F. Günthard

Symposium S-1 (Monday) : Targeting Early Infection Events

48 Mechanisms of Early CD8 T cell Control. Jonah Sacha

49 Early nNAb treatment leading to T-cell Control. Malcolm Martin

50 Anti alpha4/beta7 Ab-mediated control. James Arthos

51 Early Intervention Therapies in humans: ART, Ab and Vax. Eugène

Kroon

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

66 Persistent Detection of HIV RNA+ cells with ART started in F1&2 vs F3-5.

Thimothy Schacker

67 CD8 T cell Responses in Treated Hyperacute HIV infection Limit HIV

Reservoir size. Zaza Ndholovu

69LB Determinants of HIV-1 Reservoir size & Long-term dynamics under

suppresive ART (Swiss Cohort). Nadine Bachmann

70 No evidence for ongoing HIV replication in Lymph Nodes during

suppressive ART. Mary Kearney

71 No residual replication in DTG intensification. Thomas Rasmussen

72 Single RMD do not increase HIV expression (A5315)

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-

infected Rhesus Monkeys. Dan Barouch.

Oral Abstract O-O9 (Wednesday) : HIV Replication, Inhibition and Restriction

117 Protective Gene Expression Signature in Response to RhCMV/SIV

Vaccine Vectors. Michael Gale

118 Cross-Species CMV Vaccination Reveals Determinants of Non-Classical T

Cells. Justic Greene

Posters

-331: LRA alters Ag processing and peptide presentation in CD4 T cells

-334/335/338: Impact of ATI on HIV reservoirs and Imm parameters

-232LB: Targeting Highly Networked CTL epitopes as a mechanisms of Elite HIV

control

-303: A novel machine-learning-guided HIV immunogen desing

-304: Correlates of HIV vaccine Trials cross-predicts vaccine efficacy

-305: MF59

-306/307: AIDVAX B/E boost

-308: Epitopes after DC-based vax trial

-309: SIV rebound after TLR7a & Vax

-310: IPROTECT1: Vac-3s

-311: iHIVARNA

-357: TLR9 therapy effect on CTL responses (trial)

-359: Vacc-4x & TLR7a trial: Gag escaped CTL epitopes

-364: Proviral landscape in HIV-1 PTC and non-controllers

-279: Phosphorylated HIV as potential CTL targets

-280: Link between mithocondrial state and CD8 T cell exhaustion

-283: IFNa enhances NK cell and CD8 antiviral activity

-522: Natural control of HIV in a SA cohort: HPTN 068

Posters

-331: LRA alters Ag processing and peptide presentation in CD4 T cells

-334/335/338: Impact of ATI on HIV reservoirs and Imm parameters

-232LB: Targeting Highly Networked CTL epitopes as a mechanisms of Elite

HIV control

-303: A novel machine-learning-guided HIV immunogen desing

-304: Correlates of HIV vaccine Trials cross-predicts vaccine efficacy

-305: MF59

-306/307: AIDVAX B/E boost

-308: Epitopes after DC-based vax trial

-309: SIV rebound after TLR7a & Vax

-310: IPROTECT1: Vac-3s

-311: iHIVARNA

-357: TLR9 therapy effect on CTL responses (trial)

-359: Vacc-4x & TLR7a trial: Gag escaped CTL epitopes

-364: Proviral landscape in HIV-1 PTC and non-controllers

-279: Phosphorylated HIV as potential CTL targets

-280: Link between mithocondrial state and CD8 T cell exhaustion

-283: IFNa enhances NK cell and CD8 antiviral activity

-522: Natural control of HIV in a SA cohort: HPTN 068

Symposium S-1 (Monday) : Targeting Early Infection Events

48 Mechanisms of Early CD8 T cell Control. Jonah Sacha

Symposium S-1 (Monday) : Targeting Early Infection Events

48 Mechanisms of Early CD8 T cell Control. Jonah Sacha

Symposium S-1 (Monday) : Targeting Early Infection Events

48 Mechanisms of Early CD8 T cell Control. Jonah Sacha

Symposium S-1 (Monday) : Targeting Early Infection Events

48 Mechanisms of Early CD8 T cell Control. Jonah Sacha

Symposium S-1 (Monday) : Targeting Early Infection Events

48 Mechanisms of Early CD8 T cell Control. Jonah Sacha

Symposium S-1 (Monday) : Targeting Early Infection Events

48 Mechanisms of Early CD8 T cell Control. Jonah Sacha

Symposium S-1 (Monday) : Targeting Early Infection Events

48 Mechanisms of Early CD8 T cell Control. Jonah Sacha

Symposium S-1 (Monday) : Targeting Early Infection Events

48 Mechanisms of Early CD8 T cell Control. Jonah Sacha

Symposium S-1 (Monday) : Targeting Early Infection Events

48 Mechanisms of Early CD8 T cell Control. Jonah Sacha

Symposium S-1 (Monday) : Targeting Early Infection Events

51 Early Intervention Therapies in humans: ART, Ab and Vax. Eugène Kroon

Symposium S-1 (Monday) : Targeting Early Infection Events

51 Early Intervention Therapies in humans: ART, Ab and Vax. Eugène Kroon

Symposium S-1 (Monday) : Targeting Early Infection Events

51 Early Intervention Therapies in humans: ART, Ab and Vax. Eugène Kroon

Symposium S-1 (Monday) : Targeting Early Infection Events

51 Early Intervention Therapies in humans: ART, Ab and Vax. Eugène Kroon

Symposium S-1 (Monday) : Targeting Early Infection Events

51 Early Intervention Therapies in humans: ART, Ab and Vax. Eugène Kroon

Symposium S-1 (Monday) : Targeting Early Infection Events

51 Early Intervention Therapies in humans: ART, Ab and Vax. Eugène Kroon

Symposium S-1 (Monday) : Targeting Early Infection Events

51 Early Intervention Therapies in humans: ART, Ab and Vax. Eugène Kroon

Symposium S-1 (Monday) : Targeting Early Infection Events

51 Early Intervention Therapies in humans: ART, Ab and Vax. Eugène Kroon

Symposium S-1 (Monday) : Targeting Early Infection Events

51 Early Intervention Therapies in humans: ART, Ab and Vax. Eugène Kroon

Symposium S-1 (Monday) : Targeting Early Infection Events

51 Early Intervention Therapies in humans: ART, Ab and Vax. Eugène Kroon

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

67 CD8 T cell Responses in Treated Hyperacute HIV infection Limit HIV

Reservoir size. Zaza Ndholovu

FRESH (Sudáfrica)

Mujeres 18-23 Test HIV RNA -finger print- 2 veces por semana

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

67 CD8 T cell Responses in Treated Hyperacute HIV infection Limit HIV

Reservoir size. Zaza Ndholovu

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

67 CD8 T cell Responses in Treated Hyperacute HIV infection Limit HIV

Reservoir size. Zaza Ndholovu

VCD : Viremia copy days

Especificidad del tetramero?

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

67 CD8 T cell Responses in Treated Hyperacute HIV infection Limit HIV

Reservoir size. Zaza Ndholovu

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

67 CD8 T cell Responses in Treated Hyperacute HIV infection Limit HIV

Reservoir size. Zaza Ndholovu

CD4 Help! Capacidad

proliferativa CD8 depende de CD4!

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

67 CD8 T cell Responses in Treated Hyperacute HIV infection Limit HIV

Reservoir size. Zaza Ndholovu

CD4 Help! Capacidad

proliferativa CD8 depende de CD4!

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

67 CD8 T cell Responses in Treated Hyperacute HIV infection Limit HIV

Reservoir size. Zaza Ndholovu

Relación Respuesta CD8 con niveles de reservorio al año del cART

Hasta ahora no objetivado en tratamiento durante infección crónica

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

Barouch, Nature 2013

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

Borducci, Nature 2016

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

ART at day 7

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

No blips durante infusiones PGT121 o TLR7a. Activación CD4 (CD69+) en grupos de TLR7a No respuestas CD8 IFNg CD8 a Gag/Pol/Env en ninguno de los grupos (Early_cART)

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

Reducción de reservorio en tejido en PGT121 y combinación

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

Oral Abstract O-O5 (Tuesday) : The HIV Reservoir and Viral replication.

73LB PGT121 combined with GS-9620 delays viral rebound in SHIV-infected

Rhesus Monkeys. Dan Barouch.

Otro modelo de infección? Sin Acute_cART? Otros Ab +/- inmunomoduladores?

Oral Abstract O-O9 (Wednesday) : HIV Replication, Inhibition and Restriction

117 Protective Gene Expression Signature in Response to RhCMV/SIV

Vaccine Vectors. Michael Gale

Oral Abstract O-O9 (Wednesday) : HIV Replication, Inhibition and Restriction

117 Protective Gene Expression Signature in Response to RhCMV/SIV

Vaccine Vectors. Michael Gale

Oral Abstract O-O9 (Wednesday) : HIV Replication, Inhibition and Restriction

117 Protective Gene Expression Signature in Response to RhCMV/SIV

Vaccine Vectors. Michael Gale

Oral Abstract O-O9 (Wednesday) : HIV Replication, Inhibition and Restriction

117 Protective Gene Expression Signature in Response to RhCMV/SIV

Vaccine Vectors. Michael Gale

Oral Abstract O-O9 (Wednesday) : HIV Replication, Inhibition and Restriction

117 Protective Gene Expression Signature in Response to RhCMV/SIV

Vaccine Vectors. Michael Gale

Oral Abstract O-O9 (Wednesday) : HIV Replication, Inhibition and Restriction

117 Protective Gene Expression Signature in Response to RhCMV/SIV

Vaccine Vectors. Michael Gale

Posters

-331: LRA alters Ag processing and peptide presentation in CD4 T cells

-334/335/338: Impact of ATI on HIV reservoirs and Imm parameters

-232LB: Targeting Highly Networked CTL epitopes as a mechanisms of Elite

HIV control

-303: A novel machine-learning-guided HIV immunogen desing

-304: Correlates of HIV vaccine Trials cross-predicts vaccine efficacy

-305: MF59

-306/307: AIDVAX B/E boost

-308: Epitopes after DC-based vax trial

-309: SIV rebound after TLR7a & Vax

-310: IPROTECT1: Vac-3s

-311: iHIVARNA

-357: TLR9 therapy effect on CTL responses (trial)

-359: Vacc-4x & TLR7a trial: Gag escaped CTL epitopes

-364: Proviral landscape in HIV-1 PTC and non-controllers

-279: Phosphorylated HIV as potential CTL targets

-280: Link between mithocondrial state and CD8 T cell exhaustion

-283: IFNa enhances NK cell and CD8 antiviral activity

-522: Natural control of HIV in a SA cohort: HPTN 068

Posters

-334/335/338: Impact of ATI on HIV reservoirs and Imm parameters

334: Pacientes de estudio Ab. Infección crónica, suprimidos ++. ATI media 57d

Proviral DNA = CA-RNA = Agotamiento (PD1/TIGIT) = Marcadores activación =

Posters

-334/335/338: Impact of ATI on HIV reservoirs and Imm parameters

335: Pacientes de estudios con ATI de ACTG. medido con HIDE (DNA integrado)

338: Pacientes del A5340 (VRC01). Infección crónica, suprimidos >4 años. ATI 5

semanas en viremia mediana

DNA proviral = CA-RNA = IPUM =

En Early_cART? Escape CTL?

Posters

-232LB: Targeting Highly Networked CTL epitopes as a mechanisms of Elite

HIV control

Posters

-232LB: Targeting Highly Networked CTL epitopes as a mechanisms of Elite

HIV control

Posters

-232LB: Targeting Highly Networked CTL epitopes as a mechanisms of Elite

HIV control

Posters

-308: Epitopes after DC-based vax trial

-359: Vacc-4x & TLR7a trial: Gag escaped CTL epitopes

Posters

-308: Epitopes after DC-based vax trial

-359: Vacc-4x & TLR7a trial: Gag escaped CTL epitopes

Ningún efecto de presión inmunológica en las secuencias

Evidencia de escape pre-existente a epítopos incluidos en Vacc-4x

Posters

-311: iHIVARNA

Programa de vacuna mRNA administrada intranodal que expresa:

-Trimix (CD40L, CD70, caTLR4) –señales activación CD

-Inmunógeno HTI

Fase I (escalado de dosis) Fase II/PoC con ATI Combinación con Ab y LRA

FP7 iHIVARNA H2020 HIVACAR

Posters

-311: iHIVARNA

Fase I (escalado de dosis)

Posters

-311: iHIVARNA

Respuesta IFNg en grupo dosis máxima

Posters

-311: iHIVARNA

No cambios en DNA, ligeros en CA-HIV RNA y SCA – sugiriendo activación

transcripción en grupos de dosis mayor

CONCLUSIONES

Estudios de respuesta inmunitaria durante tratamiento durante infección

aguda/reciente del VIH identifican la respuesta CTL como factor adicional al

ART en el establecimiento de un reservorio bajo oportunidad para

estrategias de vacunación/terapias combinadas

Estudios en macacos con vacunas RhCMV y rol de la respuesta CD8 no-

convencional mediada por HLA-E. Valor de estudios de transcriptómica para

el descubrimiento de correlatos de control.

Estudio en macacos con cART en infección hiperaguda con PGT121 e

inmunomodulador como estrategia para cura funcional? Abre la posibilidad a

estudios combinación que incluyan los Ab.

ATI breves (en pacientes suprimidos durante infección crónica) seguras y sin

impacto en reservorio, marcadores de activación o agotamiento tras la

resupresión

Pocos candidatos en fase clínica, y todavía sin datos de eficacia

(Ad26/MVA.mosaicos) o iHIVARNA