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Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis

Author

Listed:
  • David A. Spencer

    (Oregon National Primate Research Center, Oregon Health & Science University
    Absci Corp)

  • Benjamin S. Goldberg

    (Dartmouth College)

  • Shilpi Pandey

    (Oregon National Primate Research Center, Oregon Health & Science University)

  • Tracy Ordonez

    (Oregon National Primate Research Center, Oregon Health & Science University)

  • Jérémy Dufloo

    (Institut Pasteur
    University of Valencia-CSIC)

  • Philip Barnette

    (Oregon National Primate Research Center, Oregon Health & Science University)

  • William F. Sutton

    (Oregon National Primate Research Center, Oregon Health & Science University)

  • Heidi Henderson

    (Oregon National Primate Research Center, Oregon Health & Science University)

  • Rebecca Agnor

    (Oregon Health & Science University)

  • Lina Gao

    (Oregon Health & Science University)

  • Timothée Bruel

    (Institut Pasteur
    Vaccine Research Institute)

  • Olivier Schwartz

    (Institut Pasteur
    Vaccine Research Institute)

  • Nancy L. Haigwood

    (Oregon National Primate Research Center, Oregon Health & Science University
    Oregon Health & Science University)

  • Margaret E. Ackerman

    (Dartmouth College)

  • Ann J. Hessell

    (Oregon National Primate Research Center, Oregon Health & Science University)

Abstract

Increasingly, antibodies are being used to treat and prevent viral infections. In the context of HIV, efficacy is primarily attributed to dose-dependent neutralization potency and to a lesser extent Fc-mediated effector functions. It remains unclear whether augmenting effector functions of broadly neutralizing antibodies (bNAbs) may improve their clinical potential. Here, we use bNAb 10E8v4 targeting the membrane external proximal region (MPER) to examine the role of antibody-mediated effector and complement (C’) activity when administered prophylactically against SHIV challenge in rhesus macaques. With sub-protective dosing, we find a 78–88% reduction in post-acute viremia that is associated with 10E8v4-mediated phagocytosis acting at the time of challenge. Neither plasma nor tissue viremic outcomes in vivo is improved with an Fc-modified variant of 10E8v4 enhanced for C’ functions as determined in vitro. These results suggest that effector functions inherent to unmodified 10E8v4 contribute to efficacy against SHIVSF162P3 in the absence of plasma neutralizing titers, while C’ functions are dispensable in this setting, informing design of bNAb modifications for improving protective efficacy.

Suggested Citation

  • David A. Spencer & Benjamin S. Goldberg & Shilpi Pandey & Tracy Ordonez & Jérémy Dufloo & Philip Barnette & William F. Sutton & Heidi Henderson & Rebecca Agnor & Lina Gao & Timothée Bruel & Olivier Sc, 2022. "Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28250-7
    DOI: 10.1038/s41467-022-28250-7
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    References listed on IDEAS

    as
    1. Ann J. Hessell & Lars Hangartner & Meredith Hunter & Carin E. G. Havenith & Frank J. Beurskens & Joost M. Bakker & Caroline M. S. Lanigan & Gary Landucci & Donald N. Forthal & Paul W. H. I. Parren & P, 2007. "Fc receptor but not complement binding is important in antibody protection against HIV," Nature, Nature, vol. 449(7158), pages 101-104, September.
    2. Xiping Wei & Julie M. Decker & Shuyi Wang & Huxiong Hui & John C. Kappes & Xiaoyun Wu & Jesus F. Salazar-Gonzalez & Maria G. Salazar & J. Michael Kilby & Michael S. Saag & Natalia L. Komarova & Martin, 2003. "Antibody neutralization and escape by HIV-1," Nature, Nature, vol. 422(6929), pages 307-312, March.
    3. Ping Zhu & Jun Liu & Julian Bess & Elena Chertova & Jeffrey D. Lifson & Henry Grisé & Gilad A. Ofek & Kenneth A. Taylor & Kenneth H. Roux, 2006. "Distribution and three-dimensional structure of AIDS virus envelope spikes," Nature, Nature, vol. 441(7095), pages 847-852, June.
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