Continued Decay of HIV Proviral DNA Upon Vaccination With HIV-1 Tat of Subjects on Long-Term ART: An 8-Year Follow-Up Study

Cecilia Sgadari; Paolo Monini; Antonella Tripiciano; Orietta Picconi; Anna Casabianca; Chiara Orlandi; Sonia Moretti; Vittorio Francavilla; Angela Arancio; Giovanni Paniccia; Massimo Campagna; Stefania Bellino; Marianna Meschiari; Silvia Nozza; Laura Sighinolfi; Alessandra Latini; Antonio Muscatello; Annalisa Saracino; Massimo Di Pietro; Massimo Galli; Aurelio Cafaro; Mauro Magnani; Fabrizio Ensoli; Barbara Ensoli

doi:10.3389/fimmu.2019.00233

Continued Decay of HIV Proviral DNA Upon Vaccination With HIV-1 Tat of Subjects on Long-Term ART: An 8-Year Follow-Up Study

Cecilia Sgadari, Paolo Monini, Antonella Tripiciano, Orietta Picconi, Anna Casabianca, Chiara Orlandi, Sonia Moretti, Vittorio Francavilla, Angela Arancio, Giovanni Paniccia, Massimo Campagna, Stefania Bellino, Marianna Meschiari, Silvia Nozza, Laura Sighinolfi, Alessandra Latini, Antonio Muscatello, Annalisa Saracino, Massimo Di Pietro, Massimo GalliAurelio Cafaro, Mauro Magnani, Fabrizio Ensoli, Barbara Ensoli

Research output: Contribution to journal › Article › peer-review

Abstract

Introduction: Tat, a key HIV virulence protein, has been targeted for the development of a therapeutic vaccine aimed at cART intensification. Results from phase II clinical trials in Italy (ISS T-002) and South Africa (ISS T-003) indicated that Tat vaccination promotes increases of CD4(+) T-cells and return to immune homeostasis while reducing the virus reservoir in chronically cART-treated patients. Here we present data of 92 vaccinees (59 enrolled in the ISS T-002 8-year extended follow-up study (ISS T-002 EF-UP, ClinicalTrials. gov NCT02118168). Results: Anti-Tat antibodies (Abs) induced upon vaccination persisted for the entire follow-up in 34/92 (37 vaccinees, particularly when all 3 Ab classes (A/G/M) were present (66, as most frequently observed with Tat 30 mu g regimens. CD4+T cells increased above study-entry levels reaching a stable plateau at year 5 post-vaccination, with the highest increase (165 cells/mu L) in the Tat 30 mu g, 3x regimen. CD4(+)T-cell increase occurred even in subjects with CD4(+)nadir

Original language	English
Journal	Front. Immunol.
Volume	10
DOIs	https://doi.org/10.3389/fimmu.2019.00233
Publication status	Published - Feb 13 2019

Keywords

HIV therapeutic vaccine
Tat
cART
anti-Tat antibodies
CD4(+) T cells
CD4(+)/CD8(+) T-cell ratio
proviral DNA
HIV reservoirs

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10.3389/fimmu.2019.00233

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Sgadari, C., Monini, P., Tripiciano, A., Picconi, O., Casabianca, A., Orlandi, C., Moretti, S., Francavilla, V., Arancio, A., Paniccia, G., Campagna, M., Bellino, S., Meschiari, M., Nozza, S., Sighinolfi, L., Latini, A., Muscatello, A., Saracino, A., Di Pietro, M., ... Ensoli, B. (2019). Continued Decay of HIV Proviral DNA Upon Vaccination With HIV-1 Tat of Subjects on Long-Term ART: An 8-Year Follow-Up Study. Front. Immunol., 10. https://doi.org/10.3389/fimmu.2019.00233

Sgadari, C , Monini, P , Tripiciano, A, Picconi, O, Casabianca, A, Orlandi, C, Moretti, S , Francavilla, V , Arancio, A , Paniccia, G , Campagna, M , Bellino, S, Meschiari, M, Nozza, S, Sighinolfi, L, Latini, A , Muscatello, A, Saracino, A, Di Pietro, M, Galli, M, Cafaro, A, Magnani, M, Ensoli, F & Ensoli, B 2019, 'Continued Decay of HIV Proviral DNA Upon Vaccination With HIV-1 Tat of Subjects on Long-Term ART: An 8-Year Follow-Up Study', Front. Immunol., vol. 10. https://doi.org/10.3389/fimmu.2019.00233

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title = "Continued Decay of HIV Proviral DNA Upon Vaccination With HIV-1 Tat of Subjects on Long-Term ART: An 8-Year Follow-Up Study",

abstract = "Introduction: Tat, a key HIV virulence protein, has been targeted for the development of a therapeutic vaccine aimed at cART intensification. Results from phase II clinical trials in Italy (ISS T-002) and South Africa (ISS T-003) indicated that Tat vaccination promotes increases of CD4(+) T-cells and return to immune homeostasis while reducing the virus reservoir in chronically cART-treated patients. Here we present data of 92 vaccinees (59 enrolled in the ISS T-002 8-year extended follow-up study (ISS T-002 EF-UP, ClinicalTrials. gov NCT02118168). Results: Anti-Tat antibodies (Abs) induced upon vaccination persisted for the entire follow-up in 34/92 (37 vaccinees, particularly when all 3 Ab classes (A/G/M) were present (66, as most frequently observed with Tat 30 mu g regimens. CD4+T cells increased above study-entry levels reaching a stable plateau at year 5 post-vaccination, with the highest increase (165 cells/mu L) in the Tat 30 mu g, 3x regimen. CD4(+)T-cell increase occurred even in subjects with CD4(+)nadir ",

keywords = "HIV therapeutic vaccine, Tat, cART, anti-Tat antibodies, CD4(+) T cells, CD4(+)/CD8(+) T-cell ratio, proviral DNA, HIV reservoirs",

author = "Cecilia Sgadari and Paolo Monini and Antonella Tripiciano and Orietta Picconi and Anna Casabianca and Chiara Orlandi and Sonia Moretti and Vittorio Francavilla and Angela Arancio and Giovanni Paniccia and Massimo Campagna and Stefania Bellino and Marianna Meschiari and Silvia Nozza and Laura Sighinolfi and Alessandra Latini and Antonio Muscatello and Annalisa Saracino and {Di Pietro}, Massimo and Massimo Galli and Aurelio Cafaro and Mauro Magnani and Fabrizio Ensoli and Barbara Ensoli",

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doi = "10.3389/fimmu.2019.00233",

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T1 - Continued Decay of HIV Proviral DNA Upon Vaccination With HIV-1 Tat of Subjects on Long-Term ART: An 8-Year Follow-Up Study

AU - Sgadari, Cecilia

AU - Monini, Paolo

AU - Tripiciano, Antonella

AU - Picconi, Orietta

AU - Casabianca, Anna

AU - Orlandi, Chiara

AU - Moretti, Sonia

AU - Francavilla, Vittorio

AU - Arancio, Angela

AU - Paniccia, Giovanni

AU - Campagna, Massimo

AU - Bellino, Stefania

AU - Meschiari, Marianna

AU - Nozza, Silvia

AU - Sighinolfi, Laura

AU - Latini, Alessandra

AU - Muscatello, Antonio

AU - Saracino, Annalisa

AU - Di Pietro, Massimo

AU - Galli, Massimo

AU - Cafaro, Aurelio

AU - Magnani, Mauro

AU - Ensoli, Fabrizio

AU - Ensoli, Barbara

PY - 2019/2/13

Y1 - 2019/2/13

N2 - Introduction: Tat, a key HIV virulence protein, has been targeted for the development of a therapeutic vaccine aimed at cART intensification. Results from phase II clinical trials in Italy (ISS T-002) and South Africa (ISS T-003) indicated that Tat vaccination promotes increases of CD4(+) T-cells and return to immune homeostasis while reducing the virus reservoir in chronically cART-treated patients. Here we present data of 92 vaccinees (59 enrolled in the ISS T-002 8-year extended follow-up study (ISS T-002 EF-UP, ClinicalTrials. gov NCT02118168). Results: Anti-Tat antibodies (Abs) induced upon vaccination persisted for the entire follow-up in 34/92 (37 vaccinees, particularly when all 3 Ab classes (A/G/M) were present (66, as most frequently observed with Tat 30 mu g regimens. CD4+T cells increased above study-entry levels reaching a stable plateau at year 5 post-vaccination, with the highest increase (165 cells/mu L) in the Tat 30 mu g, 3x regimen. CD4(+)T-cell increase occurred even in subjects with CD4(+)nadir

AB - Introduction: Tat, a key HIV virulence protein, has been targeted for the development of a therapeutic vaccine aimed at cART intensification. Results from phase II clinical trials in Italy (ISS T-002) and South Africa (ISS T-003) indicated that Tat vaccination promotes increases of CD4(+) T-cells and return to immune homeostasis while reducing the virus reservoir in chronically cART-treated patients. Here we present data of 92 vaccinees (59 enrolled in the ISS T-002 8-year extended follow-up study (ISS T-002 EF-UP, ClinicalTrials. gov NCT02118168). Results: Anti-Tat antibodies (Abs) induced upon vaccination persisted for the entire follow-up in 34/92 (37 vaccinees, particularly when all 3 Ab classes (A/G/M) were present (66, as most frequently observed with Tat 30 mu g regimens. CD4+T cells increased above study-entry levels reaching a stable plateau at year 5 post-vaccination, with the highest increase (165 cells/mu L) in the Tat 30 mu g, 3x regimen. CD4(+)T-cell increase occurred even in subjects with CD4(+)nadir

KW - HIV therapeutic vaccine

KW - Tat

KW - cART

KW - anti-Tat antibodies

KW - CD4(+) T cells

KW - CD4(+)/CD8(+) T-cell ratio

KW - proviral DNA

KW - HIV reservoirs

U2 - 10.3389/fimmu.2019.00233

DO - 10.3389/fimmu.2019.00233

M3 - Article

VL - 10

JO - Front. Immunol.

JF - Front. Immunol.

SN - 1664-3224

ER -

Continued Decay of HIV Proviral DNA Upon Vaccination With HIV-1 Tat of Subjects on Long-Term ART: An 8-Year Follow-Up Study

Abstract

Keywords

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