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Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques

Author

Listed:
  • Victoria E. K. Walker-Sperling

    (Beth Israel Deaconess Medical Center)

  • Noe B. Mercado

    (Beth Israel Deaconess Medical Center)

  • Abishek Chandrashekar

    (Beth Israel Deaconess Medical Center)

  • Erica N. Borducchi

    (Beth Israel Deaconess Medical Center)

  • Jinyan Liu

    (Beth Israel Deaconess Medical Center)

  • Joseph P. Nkolola

    (Beth Israel Deaconess Medical Center)

  • Mark Lewis

    (Bioqual)

  • Jeffrey P. Murry

    (Gilead Sciences)

  • Yunling Yang

    (Gilead Sciences)

  • Romas Geleziunas

    (Gilead Sciences)

  • Merlin L. Robb

    (Walter Reed Army Institute of Research)

  • Nelson L. Michael

    (Walter Reed Army Institute of Research)

  • Maria G. Pau

    (Janssen Vaccines & Prevention)

  • Frank Wegmann

    (Janssen Vaccines & Prevention)

  • Hanneke Schuitemaker

    (Janssen Vaccines & Prevention)

  • Emily J. Fray

    (Johns Hopkins University School of Medicine)

  • Mithra R. Kumar

    (Johns Hopkins University School of Medicine)

  • Janet D. Siliciano

    (Johns Hopkins University School of Medicine)

  • Robert F. Siliciano

    (Johns Hopkins University School of Medicine)

  • Dan H. Barouch

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

Abstract

The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control or delayed viral rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- or SHIV-infected rhesus macaques. Here we show that the combination of active and passive immunization with vesatolimod may lead to higher rates of post-ART virologic control compared to either approach alone. Therapeutic Ad26/MVA vaccination and PGT121 administration together with TLR7 stimulation with vesatolimod resulted in 70% post-ART virologic control in SHIV-SF162P3-infected rhesus macaques. These data suggest the potential of combining active and passive immunization targeting different immunologic mechanisms as an HIV-1 cure strategy.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31196-5
    DOI: 10.1038/s41467-022-31196-5
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    References listed on IDEAS

    as
    1. 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.
    2. Yoshiaki Nishimura & Rajeev Gautam & Tae-Wook Chun & Reza Sadjadpour & Kathryn E. Foulds & Masashi Shingai & Florian Klein & Anna Gazumyan & Jovana Golijanin & Mitzi Donaldson & Olivia K. Donau & Rona, 2017. "Early antibody therapy can induce long-lasting immunity to SHIV," Nature, Nature, vol. 543(7646), pages 559-563, March.
    3. Anthony M. Cadena & John D. Ventura & Peter Abbink & Erica N. Borducchi & Hubert Tuyishime & Noe B. Mercado & Victoria Walker-Sperling & Mazuba Siamatu & Po-Ting Liu & Abishek Chandrashekar & Joseph P, 2021. "Persistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    4. Erica N. Borducchi & Crystal Cabral & Kathryn E. Stephenson & Jinyan Liu & Peter Abbink & David Ng’ang’a & Joseph P. Nkolola & Amanda L. Brinkman & Lauren Peter & Benjamin C. Lee & Jessica Jimenez & D, 2016. "Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys," Nature, Nature, vol. 540(7632), pages 284-287, December.
    5. 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. "Publisher Correction: Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys," Nature, Nature, vol. 564(7734), pages 8-8, December.
    6. James B. Whitney & Alison L. Hill & Srisowmya Sanisetty & Pablo Penaloza-MacMaster & Jinyan Liu & Mayuri Shetty & Lily Parenteau & Crystal Cabral & Jennifer Shields & Stephen Blackmore & Jeffrey Y. Sm, 2014. "Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys," Nature, Nature, vol. 512(7512), pages 74-77, August.
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