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Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys

Author

Listed:
  • Erica N. Borducchi

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Jinyan Liu

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Joseph P. Nkolola

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Anthony M. Cadena

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Wen-Han Yu

    (Ragon Institute of MGH, MIT, and Harvard)

  • Stephanie Fischinger

    (Ragon Institute of MGH, MIT, and Harvard)

  • Thomas Broge

    (Ragon Institute of MGH, MIT, and Harvard)

  • Peter Abbink

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Noe B. Mercado

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Abishek Chandrashekar

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • David Jetton

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Lauren Peter

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Katherine McMahan

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Edward T. Moseley

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Elena Bekerman

    (Gilead Sciences)

  • Joseph Hesselgesser

    (Gilead Sciences)

  • Wenjun Li

    (University of Massachusetts Medical School)

  • Mark G. Lewis

    (Bioqual)

  • Galit Alter

    (Ragon Institute of MGH, MIT, and Harvard)

  • Romas Geleziunas

    (Gilead Sciences)

  • Dan H. Barouch

    (Beth Israel Deaconess Medical Center, Harvard Medical School
    Ragon Institute of MGH, MIT, and Harvard)

Abstract

The latent viral reservoir is the critical barrier for the development of a cure for HIV-1 infection. Previous studies have shown direct antiviral activity of potent HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) administered when antiretroviral therapy (ART) was discontinued, but it remains unclear whether bNAbs can target the viral reservoir during ART. Here we show that administration of the V3 glycan-dependent bNAb PGT121 together with the Toll-like receptor 7 (TLR7) agonist vesatolimod (GS-9620) during ART delayed viral rebound following discontinuation of ART in simian–human immunodeficiency virus (SHIV)-SF162P3-infected rhesus monkeys in which ART was initiated during early acute infection. Moreover, in the subset of monkeys that were treated with both PGT121 and GS-9620 and that did not show viral rebound after discontinuation of ART, adoptive transfer studies and CD8-depletion studies also did not reveal virus. These data demonstrate the potential of bNAb administration together with innate immune stimulation as a possible strategy for targeting the viral reservoir.

Suggested Citation

  • Erica N. Borducchi & Jinyan Liu & Joseph P. Nkolola & Anthony M. Cadena & Wen-Han Yu & Stephanie Fischinger & Thomas Broge & Peter Abbink & Noe B. Mercado & Abishek Chandrashekar & David Jetton & Laur, 2018. "Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys," Nature, Nature, vol. 563(7731), pages 360-364, November.
    • Handle: RePEc:nat:nature:v:563:y:2018:i:7731:d:10.1038_s41586-018-0600-6
    DOI: 10.1038/s41586-018-0600-6
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    Citations

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    Cited by:

    1. Xiaolei Wang & Eunice Vincent & Summer Siddiqui & Katherine Turnbull & Hong Lu & Robert Blair & Xueling Wu & Meagan Watkins & Widade Ziani & Jiasheng Shao & Lara A. Doyle-Meyers & Kasi E. Russell-Lodr, 2022. "Early treatment regimens achieve sustained virologic remission in infant macaques infected with SIV at birth," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Miriam Rosás-Umbert & Jesper D. Gunst & Marie H. Pahus & Rikke Olesen & Mariane Schleimann & Paul W. Denton & Victor Ramos & Adam Ward & Natalie N. Kinloch & Dennis C. Copertino & Tuixent Escribà & An, 2022. "Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Victoria E. K. Walker-Sperling & Noe B. Mercado & Abishek Chandrashekar & Erica N. Borducchi & Jinyan Liu & Joseph P. Nkolola & Mark Lewis & Jeffrey P. Murry & Yunling Yang & Romas Geleziunas & Merlin, 2022. "Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques," Nature Communications, Nature, vol. 13(1), pages 1-8, December.

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