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Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV neutralizing antibody

  1. Author:
    Asokan, Mangaiarkarasi [ORCID]
    Dias, Joana
    Liu, Cuiping
    Maximova, Anna
    Ernste, Keenan [ORCID]
    Pegu, Amarendra [ORCID]
    McKee, Krisha
    Shi, Wei
    Chen, Xuejun
    Almasri, Cassandra
    Promsote, Wanwisa
    Ambrozak, David R
    Gama, Lucio
    Hu, Jianfei
    Douek, Daniel C
    Todd, John-Paul
    Lifson,Jeffrey
    Fourati, Slim [ORCID]
    Sekaly, Rafick P
    Crowley, Andrew R
    Ackerman, Margaret E [ORCID]
    Ko, Sung Hee
    Kilam, Divya
    Boritz, Eli A
    Liao, Laura E [ORCID]
    Best, Katharine
    Perelson, Alan S [ORCID]
    Mascola, John R
    Koup, Richard A [ORCID]

  2. Author Address

    Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892; asokan.mangaiarkarasi@nih.gov rkoup@mail.nih.gov., Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892., Virology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892., Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892., Translational Research Program, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892., AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701., Department of Pathology, Case Western Reserve University, Cleveland, OH 44106., Thayer School of Engineering, Dartmouth College, Hanover, NH 03755., Virus Persistence and Dynamics Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892., Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545., Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892; asokan.mangaiarkarasi@nih.gov rkoup@mail.nih.gov.,
    1. Year: 2020
    2. Date: AUG 4
    3. Epub Date: 2020 07 20
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 117
    2. 31
    3. Pages: 18754-18763
  4. Type of Article: Article
  5. ISSN: 0027-8424
  1. Abstract:

    Treatment of HIV infection with either antiretroviral (ARV) therapy or neutralizing monoclonal antibodies (NAbs) leads to a reduction in HIV plasma virus. Both ARVs and NAbs prevent new rounds of viral infection, but NAbs may have the additional capacity to accelerate the loss of virus-infected cells through Fc gamma receptor (Fc?R)-mediated effector functions, which should affect the kinetics of plasma-virus decline. Here, we formally test the role of effector function in vivo by comparing the rate and timing of plasma-virus clearance in response to a single-dose treatment with either unmodified NAb or those with either reduced or augmented Fc function. When infused into viremic simian HIV (SHIV)-infected rhesus macaques, there was a 21% difference in slope of plasma-virus decline between NAb and NAb with reduced Fc function. NAb engineered to increase Fc?RIII binding and improve antibody-dependent cellular cytotoxicity (ADCC) in vitro resulted in arming of effector cells in vivo, yet led to viral-decay kinetics similar to NAbs with reduced Fc function. These studies show that the predominant mechanism of antiviral activity of HIV NAbs is through inhibition of viral entry, but that Fc function can contribute to the overall antiviral activity, making them distinct from standard ARVs.

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External Sources

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  2. DOI: 10.1073/pnas.2008236117
  3. PMID: 32690707
  4. View record in Web of Science®
  5. WOS: 000575439100023
  6. PII : 2008236117

Library Notes

  1. Fiscal Year: FY2019-2020
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