Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption

Wen Shi Lee, Anne B. Kristensen, Thomas A. Rasmussen, Martin Tolstrup, Lars Østergaard, Ole S. Søgaard, Bruce D. Wines, P. Mark Hogarth, Arnold Reynaldi, Miles P. Davenport, Sean Emery, Janaki Amin, David A. Cooper, Virginia L. Kan, Julie Fox, Henning Gruell, Matthew S. Parsons, Stephen J. Kent

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRAs) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC. We found that treatment with the LRA panobinostat or a short analytical treatment interruption (ATI), 21 to 59 days, was not sufficient to stimulate an increase in ADCC-competent antibodies, despite viral rebound in all subjects who underwent the short ATI. In contrast, a longer ATI, 2 to 12 months, among subjects enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial robustly boosted HIV-1 gp120-specific Fc receptor-binding antibodies and ADCC against HIV-1-infected cells in vitro. These results show that there is a lag between viral recrudescence and the boosting of ADCC antibodies, which has implications for strategies toward eliminating latently infected cells.

Original languageEnglish
Article numbere00603-17
Number of pages13
JournalJournal of Virology
Volume91
Issue number15
DOIs
Publication statusPublished - 1 Aug 2017

Keywords

  • ADCC
  • Analytical treatment interruption
  • HIV-1 cure
  • Latency
  • Latencyreversing agent
  • Panobinostat
  • SMART trial

Cite this

Lee, W. S., Kristensen, A. B., Rasmussen, T. A., Tolstrup, M., Østergaard, L., Søgaard, O. S., ... Kent, S. J. (2017). Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption. Journal of Virology, 91(15), [e00603-17]. https://doi.org/10.1128/JVI.00603-17
Lee, Wen Shi ; Kristensen, Anne B. ; Rasmussen, Thomas A. ; Tolstrup, Martin ; Østergaard, Lars ; Søgaard, Ole S. ; Wines, Bruce D. ; Mark Hogarth, P. ; Reynaldi, Arnold ; Davenport, Miles P. ; Emery, Sean ; Amin, Janaki ; Cooper, David A. ; Kan, Virginia L. ; Fox, Julie ; Gruell, Henning ; Parsons, Matthew S. ; Kent, Stephen J. / Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption. In: Journal of Virology. 2017 ; Vol. 91, No. 15.
@article{353d30689172468ebb07133cdb97e6d7,
title = "Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption",
abstract = "There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRAs) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC. We found that treatment with the LRA panobinostat or a short analytical treatment interruption (ATI), 21 to 59 days, was not sufficient to stimulate an increase in ADCC-competent antibodies, despite viral rebound in all subjects who underwent the short ATI. In contrast, a longer ATI, 2 to 12 months, among subjects enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial robustly boosted HIV-1 gp120-specific Fc receptor-binding antibodies and ADCC against HIV-1-infected cells in vitro. These results show that there is a lag between viral recrudescence and the boosting of ADCC antibodies, which has implications for strategies toward eliminating latently infected cells.",
keywords = "ADCC, Analytical treatment interruption, HIV-1 cure, Latency, Latencyreversing agent, Panobinostat, SMART trial",
author = "Lee, {Wen Shi} and Kristensen, {Anne B.} and Rasmussen, {Thomas A.} and Martin Tolstrup and Lars {\O}stergaard and S{\o}gaard, {Ole S.} and Wines, {Bruce D.} and {Mark Hogarth}, P. and Arnold Reynaldi and Davenport, {Miles P.} and Sean Emery and Janaki Amin and Cooper, {David A.} and Kan, {Virginia L.} and Julie Fox and Henning Gruell and Parsons, {Matthew S.} and Kent, {Stephen J.}",
year = "2017",
month = "8",
day = "1",
doi = "10.1128/JVI.00603-17",
language = "English",
volume = "91",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "15",

}

Lee, WS, Kristensen, AB, Rasmussen, TA, Tolstrup, M, Østergaard, L, Søgaard, OS, Wines, BD, Mark Hogarth, P, Reynaldi, A, Davenport, MP, Emery, S, Amin, J, Cooper, DA, Kan, VL, Fox, J, Gruell, H, Parsons, MS & Kent, SJ 2017, 'Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption', Journal of Virology, vol. 91, no. 15, e00603-17. https://doi.org/10.1128/JVI.00603-17

Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption. / Lee, Wen Shi; Kristensen, Anne B.; Rasmussen, Thomas A.; Tolstrup, Martin; Østergaard, Lars; Søgaard, Ole S.; Wines, Bruce D.; Mark Hogarth, P.; Reynaldi, Arnold; Davenport, Miles P.; Emery, Sean; Amin, Janaki; Cooper, David A.; Kan, Virginia L.; Fox, Julie; Gruell, Henning; Parsons, Matthew S.; Kent, Stephen J.

In: Journal of Virology, Vol. 91, No. 15, e00603-17, 01.08.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption

AU - Lee, Wen Shi

AU - Kristensen, Anne B.

AU - Rasmussen, Thomas A.

AU - Tolstrup, Martin

AU - Østergaard, Lars

AU - Søgaard, Ole S.

AU - Wines, Bruce D.

AU - Mark Hogarth, P.

AU - Reynaldi, Arnold

AU - Davenport, Miles P.

AU - Emery, Sean

AU - Amin, Janaki

AU - Cooper, David A.

AU - Kan, Virginia L.

AU - Fox, Julie

AU - Gruell, Henning

AU - Parsons, Matthew S.

AU - Kent, Stephen J.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRAs) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC. We found that treatment with the LRA panobinostat or a short analytical treatment interruption (ATI), 21 to 59 days, was not sufficient to stimulate an increase in ADCC-competent antibodies, despite viral rebound in all subjects who underwent the short ATI. In contrast, a longer ATI, 2 to 12 months, among subjects enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial robustly boosted HIV-1 gp120-specific Fc receptor-binding antibodies and ADCC against HIV-1-infected cells in vitro. These results show that there is a lag between viral recrudescence and the boosting of ADCC antibodies, which has implications for strategies toward eliminating latently infected cells.

AB - There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRAs) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC. We found that treatment with the LRA panobinostat or a short analytical treatment interruption (ATI), 21 to 59 days, was not sufficient to stimulate an increase in ADCC-competent antibodies, despite viral rebound in all subjects who underwent the short ATI. In contrast, a longer ATI, 2 to 12 months, among subjects enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial robustly boosted HIV-1 gp120-specific Fc receptor-binding antibodies and ADCC against HIV-1-infected cells in vitro. These results show that there is a lag between viral recrudescence and the boosting of ADCC antibodies, which has implications for strategies toward eliminating latently infected cells.

KW - ADCC

KW - Analytical treatment interruption

KW - HIV-1 cure

KW - Latency

KW - Latencyreversing agent

KW - Panobinostat

KW - SMART trial

UR - http://www.scopus.com/inward/record.url?scp=85023168273&partnerID=8YFLogxK

U2 - 10.1128/JVI.00603-17

DO - 10.1128/JVI.00603-17

M3 - Article

VL - 91

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 15

M1 - e00603-17

ER -

Lee WS, Kristensen AB, Rasmussen TA, Tolstrup M, Østergaard L, Søgaard OS et al. Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption. Journal of Virology. 2017 Aug 1;91(15). e00603-17. https://doi.org/10.1128/JVI.00603-17