Lars Jørgen Østergaard

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Wen Shi Lee, Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, VIC, Australia.
  • ,
  • Anne B Kristensen
  • Thomas A Rasmussen
  • ,
  • Martin Tolstrup
  • Lars Jørgen Østergaard
  • Ole S Søgaard
  • ,
  • Bruce D Wines, Department of Pathology, The University of Melbourne, VIC, Australia.
  • ,
  • P Mark Hogarth, Department of Pathology, The University of Melbourne, VIC, Australia.
  • ,
  • Arnold Reynaldi, Kirby Institute, University of New South Wales, NSW, Australia.
  • ,
  • Miles P Davenport, Kirby Institute, University of New South Wales, NSW, Australia.
  • ,
  • Sean Emery, Faculty of Medicine, University of Queensland, QLD, Australia.
  • ,
  • Janaki Amin, Kirby Institute, University of New South Wales, NSW, Australia.
  • ,
  • David A Cooper, Kirby Institute, University of New South Wales, NSW, Australia.
  • ,
  • Virginia L Kan, Infectious Diseases Section, Veterans Affair Medical Center, Washington DC, USA.
  • ,
  • Julie Fox, Department of Clinical Oncology, Guy's and St Thomas' Hospital, London, UK.
  • ,
  • Henning Gruell, Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany.
  • ,
  • Matthew S Parsons, Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, VIC, Australia.
  • ,
  • Stephen J Kent, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, VIC, Australia.

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 (LRA) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC. We find that treatment with the LRA panobinostat or a short analytical treatment interruption (ATI) of 21-59 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 of 2 to 12 months amongst 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 there is a lag between viral recrudescence and the boosting of ADCC antibodies, which has implications for strategies towards eliminating latently infected cells.IMPORTANCE The "shock and kill" HIV-1 cure strategy aims to reactivate HIV-1 expression in latently infected cells and subsequently eliminate the reactivated cells through immune-mediated killing. Several latency reversing agents (LRA) have been examined in vivo, but LRAs alone have not been able to achieve HIV-1 remission and prevent viral rebound following analytical treatment interruption (ATI). Here, we examine whether LRA treatment or ATI can provide sufficient antigenic stimulus to boost HIV-1-specific functional antibodies that can eliminate HIV-1-infected cells. Our study has implications for the antigenic stimulus required for anti-latency strategies and/or therapeutic vaccines to boost functional antibodies and assist in eliminating the latent reservoir.

Original languageEnglish
JournalJournal of Virology
ISSN0022-538X
DOIs
Publication statusPublished - Jul 2017

    Research areas

  • Journal Article

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ID: 114546852